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Review

Interleukin-6: A Central Biomarker in Adult and Pediatric Cancer and Infectious Disease

by
Giorgia Di Benedetto
1,†,
Carmen Sorice
1,†,
Immacolata Cantiello
1,
Maria Savarese
1,
Ornella Leone
1,
Michele Antonio Capozza
2,* and
Mariaevelina Alfieri
1,*
1
Clinical Pathology, Santobono-Pausilipon Children Hospital, 80123 Naples, Italy
2
UOC Oncologia Pediatrica, AORN “Santobono-Pausilipon”, Via Posillipo 226, 80123 Naples, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biologics 2026, 6(1), 5; https://doi.org/10.3390/biologics6010005
Submission received: 28 November 2025 / Revised: 16 January 2026 / Accepted: 23 January 2026 / Published: 2 February 2026
(This article belongs to the Section Cytokines and Allied Mediators)
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Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine with an essential role in immunity, inflammation, and cancer. Produced by immune, stromal and epithelial cells in response to infection or tissue stress, IL-6 regulates immune responses, acute-phase proteins (including serum amyloid A and C-reactive protein), hematopoiesis, and tissue remodeling. These effects are mediated via classical and trans-signaling pathways, which activate key intracellular cascades such as JAK/STAT3, MAPK, and PI3K/AKT. Accumulating evidence implicates dysregulated IL-6 signaling in both oncologic and infectious diseases, where it contributes to disease progression, immune evasion, and therapeutic resistance. This review aims to critically examine the role of IL-6 as a biomarker and therapeutic target in these two major clinical contexts: in cancer, IL-6 levels reflect tumor burden, prognosis, and therapy resistance in both adult and pediatric patients; in infectious diseases, circulating IL-6 may support early diagnosis and risk stratification, particularly in vulnerable pediatric populations. By integrating molecular mechanisms with clinical evidence, this review highlights IL-6 as a unifying biomarker linking inflammation, infection, and malignancy. It also addresses current limitations, including assay variability, lack of standardized reference ranges, especially in children, and challenges in clinical implementation.

1. Introduction

IL-6 was originally identified in 1986 as a B-cell stimulatory factor that promotes the differentiation of effector B cells into antibody-producing cells [1]. It is a 25–26 kDa secreted glycoprotein composed of 184 amino acids and is also referred to as interferon-β2, hepatocyte-stimulating factor, and hybridoma/plasmacytoma growth factor [2]. IL-6 is produced constitutively or upon stimulation by a wide range of cell types, including monocytes, macrophages, T and B lymphocytes, hepatocytes, endothelial cells, fibroblasts, keratinocytes, mesangial cells, adipocytes, and tumor cells [3]. Its production is typically induced under inflammatory conditions and during infection through stimulation by IL-1 and TNF-α or activation of Toll-like receptors [4]. IL-6 signaling occurs through a receptor complex composed of the IL-6 receptor α-chain (IL-6R, CD126) and the signal-transducing subunit gp130 (CD130) via two distinct mechanisms: classical signaling, limited to IL-6R-expressing cells, and trans-signaling, mediated by the soluble IL-6 receptor (sIL-6R), thereby enabling IL-6 responsiveness in nearly all gp130-expressing cells (Figure 1) [5,6,7]. While classical signaling is largely associated with regenerative and homeostatic functions, trans-signaling predominantly drives pro-inflammatory and pathological responses [8].
Activation of the IL-6/IL-6R/gp130 complex triggers multiple intracellular cascades, most notably the JAK/STAT3 pathway, as well as PI3K/AKT and RAS/MAPK signaling [9,10]. Persistent STAT3 activation promotes cell survival, angiogenesis, immune evasion, and therapy resistance, particularly in cancer [11].
Through the activation of its downstream signaling pathways, IL-6 exerts broad local and systemic effects that translate into distinct clinical manifestations. At the local level, IL-6 promotes vascular permeability, endothelial activation, and leukocyte recruitment, thereby contributing to tissue edema, pain, and organ dysfunction during acute inflammatory responses [12]. Systemically, IL-6 is a key driver of the hepatic acute-phase response, inducing the production of proteins such as C-reactive protein, serum amyloid A, fibrinogen, and hepcidin. These molecules are routinely used in clinical practice as biomarkers of inflammation, infection severity, coagulation abnormalities, and anemia of chronic disease [3].
A hallmark of IL-6 biology is its context-dependent dual role. While transient IL-6 production is essential for effective host defense, tissue repair, and regeneration, chronic or dysregulated IL-6 signaling promotes persistent inflammation, autoimmunity, fibrosis, and tissue damage, contributing to the pathogenesis of disorders such as rheumatoid arthritis, inflammatory bowel disease, and cytokine-driven malignancies [12,13].
Importantly, the biological outcome of IL-6 signaling is influenced by the mode of receptor engagement. Classical IL-6 signaling via the membrane-bound IL-6 receptor is generally associated with regenerative and homeostatic functions, whereas IL-6 trans-signaling mediated by the soluble IL-6 receptor broadens cellular responsiveness and predominantly drives pro-inflammatory and pathological processes [8]. Beyond its immunomodulatory role, IL-6 contributes to tissue remodeling, hematopoiesis, and bone metabolism. It supports keratinocyte proliferation during wound healing, enhances megakaryocyte maturation and platelet production, promotes myeloid differentiation of hematopoietic stem cells under inflammatory stress, and stimulates osteoclastogenesis, thereby linking chronic inflammation to bone loss [14,15,16,17]. In addition, IL-6 shapes adaptive immune responses by promoting the differentiation of T helper 17 (Th17) and T follicular helper cells while inhibiting regulatory T cells, ultimately skewing the immune balance toward a pro-inflammatory phenotype [18] (Figure 2).
Although IL-6 has been extensively investigated in adult inflammatory and oncologic diseases, its translation into routine clinical practice as a biomarker remains limited by methodological heterogeneity, the lack of standardized reference ranges, and inconsistent reporting of assay platforms and statistical metrics. Indeed, reference ranges for circulating IL-6 are incompletely defined and highly dependent on analytical methodology and patient-related factors. In healthy adult populations, IL-6 concentrations are generally low or undetectable and are most commonly reported below 5–7 pg/mL; however, upper limits vary according to the assay platform (e.g., ELISA, electrochemiluminescence immunoassays, or flow cytometry–based methods) and pre-analytical conditions [12,19]. In contrast, universally accepted reference values for IL-6 in pediatric populations are largely unavailable. Age-dependent immune maturation, differences in baseline inflammatory tone, and the dynamic regulation of cytokine networks during growth contribute to substantial variability in IL-6 levels across pediatric age groups [20]. Moreover, pediatric studies are frequently limited by small cohort sizes, heterogeneous disease contexts, and non-standardized sampling time points, further complicating the establishment of reliable cut-offs [21]. As a consequence, IL-6 thresholds derived from adult cohorts are often extrapolated to children, despite limited biological and methodological justification. Together, developmental immune differences and assay-dependent variability significantly limit direct comparisons between adult- and pediatric-derived IL-6 values, underscoring the need for age-specific reference ranges and harmonized measurement strategies to improve the clinical interpretability of IL-6 as a biomarker.
The purpose of this review is therefore to integrate molecular, translational, and clinical evidence on IL-6 signaling, with particular emphasis on its role as a biomarker and therapeutic target in cancer and infectious diseases, highlighting key differences between adult and pediatric populations while critically addressing current limitations and future directions.

2. IL-6 as a Biomarker and Therapeutic Target in Cancer

Interleukin-6 (IL-6) represents a key molecular nexus between inflammation and cancer progression. Predominantly secreted by tumor-associated macrophages (TAMs), IL-6 promotes tumor growth by enhancing proliferation, suppressing apoptosis, and stimulating angiogenesis, and its dysregulated production and signaling, particularly via the IL-6–JAK–STAT3 axis, have been implicated in a broad spectrum of malignancies, including breast, colon, lung, ovarian, and prostate cancers, as well as multiple myeloma [22,23]. Persistent STAT3 activation driven by IL-6 contributes to cancer stem-like cell maintenance and suppression of antitumor immunity, making this axis a major target of translational oncology efforts [24].
Recent studies have clarified how classic, trans-, and cluster IL-6 signaling activates JAK/STAT3 and other pathways, including MAPK/ERK, to upregulate immune checkpoints (notably PD-L1), reprogram myeloid and lymphoid compartments, sustain tumor-promoting inflammation and drive resistance to immunotherapy. For instance, Zhao et al. (2025) demonstrated in a translational study that IL-6 secreted by cancer-associated adipocytes upregulates PD-L1 expression on tumor cells, thereby enhancing immune escape mechanisms [25]. These mechanistic insights have fostered therapeutic strategies, with selective blockade of IL-6 trans-signaling and combination approaches with immune checkpoint inhibitors, to counter tumor progression and restore antitumor immunity [26].
Extensive clinical evidence across multiple malignancies highlights IL-6 as a key driver of tumor progression, metastasis, therapy resistance, and poor prognosis (Table 1).
However, reported circulating IL-6 levels vary substantially between studies due to differences in assay platforms, sampling timepoints, and clinical settings, with most measurements performed using enzyme-linked immunosorbent assays (ELISA), although methodological heterogeneity remains a key limitation. Notably, a large observational study published in 2025 reported that cancer patients with elevated baseline serum IL-6 levels exhibited more advanced disease and higher mortality, reinforcing its prognostic relevance across tumor types [27]. This evidence underscores that elevated IL-6 not only reflects tumor-promoting biological activity but also represents a clinically relevant biomarker for patient stratification and prognostic assessment.
Table 1. IL-6 Roles, Serum Levels, Source Cells, and Immune Checkpoints in Various Cancers.
Table 1. IL-6 Roles, Serum Levels, Source Cells, and Immune Checkpoints in Various Cancers.
Cancer TypeRole of IL-6IL-6 Levels (pg/mL)Assay MethodClinical
Implications		References
Colorectal cancerInflammation-driven progression0.7–68.0 pg/mL in patients (mean ~6.6 pg/mL); controls ~2.6 pg/mL;
cutoff 6.3 pg/mL		ELISAPoor prognosis; recurrence risk[28]
Prostate cancerSTAT3 activation, chemoresistance36.7 ± 20.8 pg/mL (non-responders) vs. 10.8 ± 9.5 pg/mL (responders)ELISAPredictor of docetaxel resistance[29]
Breast cancerTumor progression, EMT, immune evasion, therapy resistance>25.3 pg/mL in metastatic disease;
5.6–39.8 pg/mL by stage;
>15.5 pg/mL associated with higher metastasis risk		ELISAPrognostic biomarker; predictor of metastasis; marker of treatment resistance[30,31]
NSCLCTumor progression, immunotherapy resistance3.7 pg/mL (IQR 2.3–7.2) in patients vs. 2.1 pg/mL (IQR 1.4–3.8) in healthy controlsElectro-
chemiluminescence
immunoassay (ECLIA)		Prognostic and predictive biomarker for ICI response[32]
Various solid and hematologic tumorsTME remodeling, immune suppressionVariableELISA/multiplexPan-cancer prognostic biomarker[33,34,35]
In hematologic malignancies such as multiple myeloma, IL-6 acts as a critical growth factor via STAT3 activation, and its inhibition enhances the efficacy of chemotherapeutic agents, as demonstrated in both preclinical and clinical studies [36]. In colorectal cancer, elevated circulating IL-6 has consistently correlated with higher tumor stage and worse survival in observational and prospective cohorts [37,38]. Preoperative serum IL-6 levels measured by ELISA ranged from 0.7 to 68.0 pg/mL (mean 6.6 pg/mL) in patients, compared with approximately 2.6 pg/mL in healthy controls [28]. In a large prospective cohort of 1494 stage III colon cancer patients, post-surgical plasma IL-6 levels measured 3–8 weeks after surgery (median 3.8 pg/mL) were independently associated with increased recurrence and mortality over a median follow-up of 5.9 years, indicating that systemic inflammation after diagnosis is a strong prognostic factor [39]. Importantly, both epithelial IL-6R expression and stromal IL-6 localization have been linked to adverse outcomes, particularly in right-sided colorectal tumors, highlighting the importance of spatially resolved analyses in understanding IL-6 biology [40]. In solid tumors such as prostate cancer, IL-6 signaling contributes to progression and chemoresistance [41,42]. In patients receiving docetaxel, elevated baseline IL-6 levels were associated with treatment resistance, with nonresponders exhibiting higher concentrations (36.7 ± 20.8 pg/mL) than responders (10.8 ± 9.5 pg/mL; p < 0.01), supporting its potential role as a predictive biomarker of resistance [29]. Similarly, in breast cancer, multiple observational studies and meta-analyses have consistently reported a strong association between elevated circulating IL-6 and disease progression. A systematic review and meta-analysis including 1748 breast cancer patients reported a significant association between high serum IL-6 levels and reduced overall survival, with a pooled hazard ratio of 3.74 (95% CI: 1.84–7.6) [43]. Reported IL-6 concentrations vary widely depending on disease stage and clinical context, ranging from median values below 1 pg/mL in localized disease to mean levels exceeding 25 pg/mL in metastatic settings [44,45,46,47]. Notably, a prospective study identified a serum IL-6 cutoff of 15.495 pg/mL as predictive of metastatic risk, while a recent 2025 longitudinal study demonstrated that rising IL-6 levels at disease progression predicted resistance to CDK4/6 inhibitors, underscoring its utility as a dynamic, non-invasive biomarker [30,31]. In non-small-cell lung cancer (NSCLC), elevated IL-6 levels have been consistently linked to tumor progression, poor prognosis, and therapy resistance.
In a cohort of treatment-naïve lung cancer patients, median baseline serum IL-6 levels ranged from approximately 3.7 pg/mL (IQR 2.3–7.2) compared with 2.1 pg/mL (IQR 1.4–3.8) in healthy controls [32], while other cohorts reported higher mean values, reflecting population- and assay-related variability [48].
In advanced NSCLC treated with PD-1/PD-L1 inhibitors, baseline IL-6 cutoffs around 13 pg/mL have been used to stratify outcomes, with higher levels correlating with shorter progression-free and overall survival in observational and meta-analytic studies [49,50,51]. Furthermore, in EGFR-mutant NSCLC, elevated plasma IL-6 has been linked to acquired resistance to EGFR tyrosine kinase inhibitors, including osimertinib, with both clinical correlations and mechanistic validation in cell-line models [52]. Additional evidence suggests that IL-6 may influence drug metabolism and pharmacokinetics, further contributing to therapeutic resistance [53].
Collectively, despite variability in absolute IL-6 concentrations across studies, driven by differences in assay methodology, timing of sample collection, and patient populations, converging evidence from observational studies, prospective cohorts, and meta-analyses consistently supports IL-6 as a robust prognostic biomarker and a potential therapeutic target across diverse malignancies. Its clinical utility spans monitoring disease progression, predicting therapeutic response, and identifying patients at higher risk of adverse outcomes. Importantly, integrating IL-6 measurements with clinical context, disease stage, and complementary biomarkers can enhance prognostic accuracy and guide personalized treatment strategies. Emerging therapeutic approaches targeting IL-6 signaling, including blockade of classic, trans-, and cluster pathways, hold promise for improving outcomes in cancers such as breast, lung, colorectal, and hematologic malignancies, highlighting the translational relevance of IL-6 in precision oncology [33,34,35,54,55,56,57].

Challenges and Clinical Relevance of IL-6 as a Biomarker in Pediatric Cancers

While the oncogenic functions of IL-6 have been extensively characterized in adult malignancies, translating these findings to pediatric oncology requires careful consideration of fundamental biological and epidemiological differences. Pediatric cancers arise in the context of a developing immune system, distinct tumor biology, and limited cumulative environmental exposure, factors that may profoundly influence cytokine dynamics and biomarker performance. A major challenge in pediatric oncology is the absence of standardized, age-specific IL-6 reference ranges, compounded by small cohort sizes, disease rarity, and heterogeneity in assay platforms and sampling strategies. Consequently, IL-6 thresholds derived from adult studies may not be directly applicable to children, limiting their clinical interpretability. Despite these limitations, elevated IL-6 levels have been linked to disease severity, metastasis, and therapy resistance in several pediatric malignancies, including neuroblastoma, osteosarcoma, ALL, and AML (Table 2).
Importantly, most available evidence derives from observational or retrospective studies, highlighting the need for prospective, harmonized pediatric investigations integrating longitudinal cytokine profiling with clinical outcomes.
In neuroblastoma, elevated serum IL-6 concentrations are significantly correlated with reduced overall survival and an increased risk of metastatic dissemination [60]. IL-6 appears to serve both as a biomarker of disease severity and a potential contributor to therapy resistance. In patients with high-risk neuroblastoma, pretreatment peripheral blood IL-6 levels averaged 23.9 pg/mL, compared with 4.3 pg/mL in low/intermediate-risk patients and 3.3 pg/mL in healthy controls. Consistently, IL-6 levels in bone marrow were approximately 15 pg/mL in high-risk cases, but undetectable in low- or intermediate-risk disease [58]. Similarly, in pediatric osteosarcoma, elevated serum IL-6 levels have been linked to more aggressive tumor behavior; increased metastatic potential, particularly to the lungs; and an overall poorer prognosis [59,61]. Collectively, these findings support the concept that IL-6 contributes to tumor progression across multiple pediatric solid malignancies and highlight its potential as a therapeutic target in pediatric oncology.
Beyond solid tumors, IL-6 has been implicated in shaping early-life immune responses that may influence the risk of developing pediatric acute lymphoblastic leukemia (ALL). In a large cohort study, neonatal IL-6 levels did not show a consistent association with overall ALL risk, but age-stratified analyses indicated that higher IL-6 concentrations were linked to a reduced risk of ALL diagnosed between 2 and 5 years of age [20]. In contrast, in established leukemia, aberrant activation of the IL-6/STAT3 signaling axis promotes chemoresistance and enhances pro-survival pathways in leukemic cells, thereby contributing to disease persistence and progression. These observations underscore the complex and context-dependent role of IL-6 in leukemogenesis, potentially exerting protective effects during early immune development while supporting malignant cell survival at later stages.
Despite its clinical relevance, the precise role of IL-6 in the initiation, progression, and therapeutic response of pediatric ALL remains largely unexplored. There is a critical need for mechanistic studies to elucidate how IL-6 signaling influences leukemic progenitors during early life and throughout disease evolution. From a therapeutic perspective, two CD19-directed chimeric antigen receptor (CAR) T-cell therapies have been approved by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of relapsed and/or refractory B-cell ALL (B-ALL).
However, CAR T-cell therapy is frequently complicated by cytokine release syndrome (CRS), a potentially life-threatening systemic inflammatory response largely driven by excessive IL-6 production. To mitigate this toxicity, tocilizumab, a humanized monoclonal antibody targeting the IL-6 receptor (IL-6R), has been approved and is widely used as adjunctive therapy in patients experiencing moderate to severe CRS [62]. Emerging evidence suggests that prophylactic or early tocilizumab administration may not only control inflammation but also improve clinical outcomes and CAR T-cell persistence, thereby optimizing the therapeutic index of CAR T-cell therapy [63,64]. Future research should focus on integrating longitudinal cytokine profiling with functional analyses of IL-6/STAT3 signaling pathways, as well as investigating potential interactions with genetic, epigenetic, and environmental factors. Such approaches will be essential to better define the contribution of IL-6 to pediatric ALL pathophysiology and to identify novel opportunities for targeted therapeutic intervention.
In pediatric acute myeloid leukemia (AML), a study published in 2017 demonstrated that elevated IL-6 levels in the bone marrow at diagnosis were significantly associated with poor event-free survival, particularly among patients otherwise classified as low-risk. Mechanistically, enhanced IL-6-induced STAT3 signaling was observed at relapse and shown to attenuate chemotherapy-induced apoptosis in vitro, implicating IL-6 in microenvironment-mediated drug resistance. Clinically, children presenting with low IL-6 levels at diagnosis exhibited a 5-year event-free survival of 82.5% ± 11%, compared with only 17.3% ± 11% among those with elevated IL-6 concentrations (p = 0.0003) [21].
Taken together, these findings support the notion that IL-6 may act as a shared mediator of poor prognosis and treatment failure across biologically diverse pediatric malignancies. This underscores the need for systematic evaluation of IL-6 signaling in larger, harmonized clinical cohorts. A deeper understanding of the multifaceted role of IL-6 in pediatric cancers will be essential for the development of effective targeted strategies aimed at improving therapeutic responses and ultimately enhancing patient outcomes and quality of life.

3. IL-6 as a Biomarker for Gram-Negative and Gram-Positive Infections

Due to its early rise in the inflammatory cascade, IL-6 represents a promising biomarker for infection severity and a potential therapeutic target in dysregulated immune responses [65]. This is particularly relevant in bacterial bloodstream infections (BSIs), which are associated with high mortality, prolonged hospital stays, increased healthcare costs and severe clinical complications. Although microbiological cultures remain the cornerstone for sepsis diagnosis and for guiding antimicrobial therapy, their turnaround time is often too slow to meet urgent clinical needs, emphasizing the importance of rapid and reliable biomarkers such as IL-6 [66]. For this reason, cytokines have gained increasing attention as rapid and informative indicators of the host immune response.
In a prospective observational cohort study, Jingjing Guan and colleagues assessed cytokine profiles to classify bacterial infection and their clinical implications.
The cohort consisted of 55 individuals with Gram-positive (GP) BSI, 64 with Gram-negative (GN) BSI, and 52 uninfected individuals [67].
Serum IL-6, reported as absolute values or fold changes, was measured after antibiotic treatment by flow cytometry using a FACSCanto™ system based on the cytometric bead array technique.
IL-6 levels were significantly higher in the GN-BSI group than in the GP-BSI group (p = 0.010). Patients infected with Escherichia coli or Klebsiella pneumoniae showed markedly elevated IL-6 levels (median increase ranging from 4–31-fold) compared with those with Staphylococcus hominis or Staphylococcus epidermidis infections. Despite its modest sensitivity (39.1%), IL-6 demonstrated high specificity (85.5%) with an area under the curve (AUC) of 0.637, supporting its potential role as an exclusion biomarker: IL-6 < 418.9 pg/mL may help exclude Gram-negative bloodstream infections.
Higher IL-6 levels were associated with increased risks of septic shock and mortality among BSI patients. Specifically, IL-6 concentrations < 534.70 pg/mL could be considered to exclude septic shock, whereas values > 1000 pg/mL were linked to septic shock and mortality rates of 50.0% and 38.89%, respectively.
During disease remission following treatment, IL-6 levels declined significantly, with a median fold reduction of approximately tenfold in GP-BSI patients and 23-fold in GN-BSI patients (p < 0.001).
These observations underscore a significant link between IL-6 levels, illness severity, treatment response and patient outcomes, suggesting that IL-6 measurement may support early differentiation between GP-BSI and GN-BSI.
Consistent with these observations, a large retrospective cohort study by Xianggui Yang and colleagues further highlighted the diagnostic value of IL-6 in distinguishing GN-BSI from GP-BSI [68]. In this study, 505 patients with BSI were enrolled, and inflammatory markers were compared between GN-BSI and GP-BSI cases.
Serum IL-6 and IL-10 levels were measured by flow cytometry using a DxFLEX analyzer (Beckman Coulter, Brea, California USA) with reagents from Raisecare Biological Technology (Qingdao, China).
IL-6 levels were reported as median and interquartile range (IQR) and were significantly higher in GN-BSI patients (397.4 pg/mL [IQR 125.1–1447.0]) compared with GP-BSI patients (172.4 pg/mL [IQR 84.81–216.1]; p = 0.0003).
Similarly, procalcitonin (PCT) levels were significantly higher in GN-BSI patients (11.29 ng/mL [IQR 1.80–41.63]) than in GP-BSI patients (0.53 ng/mL [IQR 0.12–2.94]; p < 0.0001), and interleukin-10 (IL-10) levels were also significantly higher in GN-BSI patients (67.78 pg/mL [IQR 28.71–188.4]) than in GP-BSI patients (5.75 pg/mL [IQR 2.38–19.35]; p = 0.0105), whereas CRP values showed a more modest difference between GN-BSI and GP-BSI patients (132.2 mg/L [IQR 64.97–226.6] vs. 89.42 mg/L [IQR 47.84–183.0]; p = 0.0077).
Receiver operating characteristic (ROC) curve analysis demonstrated that IL-6, PCT, and IL-10 effectively distinguished GN-BSI from GP-BSI (AUC > 0.7), whereas CRP and other markers showed limited discriminatory power (AUC < 0.60). Optimal cut-off analysis revealed that IL-6 achieved diagnostic sensitivity > 74% and specificity > 63%.
Notably, IL-6 exhibited both higher absolute serum concentrations and a greater statistical difference between GN-BSI and GP-BSI than other biomarkers indicating a potentially central role in the inflammatory response and differential diagnosis of Gram-negative bloodstream infections. Overall, these findings reinforce IL-6 as a valuable diagnostic tool, enabling physicians to accurately identify potential pathogens and, consequently, select the most appropriate treatment in a timely manner.

IL-6 as a Biomarker for Gram-Negative and Gram-Positive Infections in Pediatric Oncologic Populations

Interestingly, similar mechanisms have been investigated in pediatric populations, particularly in immunocompromised children, where IL-6 may also play a critical role in the early detection and risk stratification of infection. Children receiving chemotherapy for cancer frequently develop febrile neutropenia, a frequent and serious complication. Profound immunosuppression makes them highly susceptible to infections, a risk further increased by the presence of indwelling vascular or urinary catheters. Early detection of these infections is often challenging, as the typical immune warning signs may be absent. However, blood biomarkers such as IL-6 can facilitate early and accurate infection detection, improving clinical management in these patients [69]. Soker and colleagues highlighted, in a limited prospective group of pediatric patients (n = 11), that IL-6 is able to distinguish between Gram-negative and Gram-positive bacterial infections. Venous blood samples were collected within 2–6 h of fever onset, and serum cytokine levels were measured using the non-RIA chemiluminescence method (Immulite, EURO/DPC Ltd., Gwynedd, UK). Median IL-6 concentrations were significantly higher in Gram-negative bacteremia (166 pg/mL, range 21–1780) than in Gram-positive infections (26 pg/mL, range 16–33; p = 0.042) [70].
These results were confirmed by Xu et al. in the most extensive prospective observational study involving 3118 fever events in children with cancer [71].
Blood samples were collected at the onset of fever and IL-6 was measured by flow cytometry using a cytometric bead array (CBA) Human Th1/Th2 Cytokine Kit II. They reported that an IL-6 level of ≥185 pg/mL independently predicted Gram-negative bacteremia (area under the curve [AUC] = 0.77, relative risk [RR] = 3.02, p < 0.001), demonstrating markedly superior performance compared to C-reactive protein (AUC = 0.56). Similarly, in a prospective observational study, Gupta’s group [69,72], measured serum IL-6 levels from blood samples collected at the onset of fever in inpatients or within 6 h of hospital presentation. Elevated IL-6 concentrations were recorded in patients with Gram-negative bacteremia (median 169 pg/mL, IQR: 124–2600) compared with non-infectious episodes (median 52 pg/mL; p = 0.017), whereas Gram-positive cases (n = 2) exhibited lower levels (median 17.5 pg/mL). CRP did not effectively discriminate between groups (GN: 60.7 mg/L; GP: 85.5 mg/L; sterile: 44.2 mg/L; p = 0.796). All microbiologically documented infection (MDI) occurred with severe neutropenia (ANC < 100/µL), and levels above 100 pg/mL were predictive of mortality. Taken together, these findings underscore the diagnostic relevance of IL-6 in immunocompromised pediatric patients, where rapid identification of infection type can critically influence outcomes, and highlight its strong association with Gram-negative infections, suggesting that integrating this biomarker into routine clinical practice could support early risk stratification, prompt detection of severe infections, and better therapeutic decision-making (Table 3).

4. IL-6 as a Potential Biomarker for the Diagnosis and Prognosis of Viral Infections

Although IL-6 is well recognized for its role in bacterial infections, increasing evidence highlights its importance in the pathophysiology of viral diseases. Acute respiratory viral infections, such as influenza A (FluA), respiratory syncytial virus (RSV), and COVID-19, may develop into severe disease requiring hospitalization and are associated with substantial illness and death. The identification of biomarkers for early detection and prognostic assessment remains a critical clinical priority [73]. In severe viral respiratory infections, circulating IL-6 levels reflect the magnitude of systemic inflammation and correlate with disease severity. Elevated IL-6 has been consistently associated with heightened immune activation and adverse clinical outcomes, making it a useful indicator of host response intensity to viral pathogens [74].
In a cross-sectional study, Iftimie et al. evaluated blood levels of IL-6, arachidonic acid, and CRP in individuals with FluA (n = 172), RSV (n = 80), and COVID-19 (n = 217) and healthy controls (n = 104). Blood samples were collected within 2 days of diagnosis for individuals with FluA or RSV and within 7 days for those with COVID-19. Serum arachidonic acid concentrations were quantified by ELISA (Elabscience Biotechnology Inc., Houston, TX, USA), IL-6 concentrations were measured using Elecsys® IL-6 immunoassay on a Cobas e801 analyzer (Roche Diagnostics, Basel, Switzerland), and CRP was evaluated using a latex-enhanced immunoturbidimetric assay on a Cobas c702 automated analyzer (Roche Diagnostics).
Across all viral infections, IL-6 and CRP levels were significantly elevated, whereas arachidonic acid levels were reduced. Distinct biomarker patterns suggested pathogen-specific immune signatures. Notably, IL-6 outperformed both arachidonic acid and CRP as a diagnostic marker, with receiver operating characteristic (ROC) curve AUC values exceeding 0.85. Moreover, IL-6 demonstrated good prognostic accuracy in distinguishing survivors from non-survivors among FluA patients (AUC = 0.80). However, none of the measured parameters effectively differentiated mild from severe or fatal cases [75]. These findings support IL-6 as a robust diagnostic biomarker and a prognostic indicator of increased mortality risk, particularly in FluA and COVID-19, where elevated levels correlate with prolonged hospitalization, complications, and higher mortality.
Further evidence for the prognostic value of IL-6 comes from studies of influenza A(H1N1)pdm09 infection. Severe and fatal outcomes in these patients are characterized by marked cytokine dysregulation, including elevated pro- and anti-inflammatory mediators [76].
Alagarasu et al. conducted a retrospective observational study and measured cytokine levels in plasma samples collected during the acute phase from fatal cases (n = 28), severe survivors (n = 28), mild recovered patients (n = 21), and healthy controls (n = 11). Plasma IL-6 levels were measured in the early stage of influenza A(H1N1)pdm09 infection (within one week of symptom onset) using a BD™ Cytometric Bead Array Th1/Th2/Th17 kit and analyzed by flow cytometry on a BD FACSCalibur™ system.
IL-6 concentrations were significantly higher in lethal cases (Mean ± SE, 812 pg/mL ± 451.3, p <0.001) and in high-risk survivors (Mean ± SE, 112.6 pg/mL ± 53, p < 0.05) relative to non-severe cases (Mean ± SE, 6.11 pg/mL ± 3.57) and unaffected individuals (Mean ± SE, 5.039 pg/mL ± 1.69), and levels were also significantly greater in fatal cases than in severe survivors [77].
These results indicate that excessive IL-6 production during the acute phase of infection is closely associated with disease severity and mortality risk, potentially contributing to viral persistence or secondary bacterial infections [78]. Accordingly, IL-6 may serve as a predictive biomarker to identify patients at higher risk of fatal outcomes and guide early therapeutic interventions (Table 4).

IL-6 as a Potential Biomarkers for the Diagnosis and Prognosis of Viral Infections in Pediatric Populations

IL-6 is also a clinically relevant biomarker in pediatric populations, particularly in cases of H1N1 influenza. Children aged 5–14 years account for a large proportion of hospitalized cases, and a subset develops severe complications such as pneumonia and acute respiratory distress syndrome (ARDS), often requiring pediatric intensive care and mechanical ventilation [81,82]. Excessive cytokine production has been proposed as a key contributor to disease severity in this age group [83].
Chiaretti et al. assessed plasma cytokine levels in children with H1N1 infection (n = 15) compared with controls with lower respiratory tract infections (n = 15).
In this prospective observational study, plasma IL-6 levels were measured at hospital admission during the acute phase of H1N1 infection using commercial immunoenzymatic kits (Human Quantikine by R&D Systems). IL-1β and IL-6 levels were significantly elevated in H1N1-infected children, with IL-6 showing a particularly pronounced increase. Importantly, higher IL-6 levels correlated with worsening respiratory function, including lower oxygen saturation at admission and higher fever [79]. These findings suggest that IL-6 is closely linked to airway inflammation and disease severity in pediatric influenza.
Beyond respiratory complications, increased IL-6 concentrations have been related with neurological manifestations of influenza in children, including febrile seizures and brain injury [84]. In a retrospective analysis conducted by Peng Li et al. including 161 children with severe influenza, serum IL-6 levels measured at the first laboratory evaluation after hospital admission (≥9.84 pg/mL), along with elevated CRP, early hospitalization, increased cerebrospinal fluid protein, and FluA infection, were identified as significant risk factors for febrile seizures [80].
These data further support the role of IL-6 as a clinically relevant biomarker for identifying pediatric patients at risk of severe complications and highlight the importance of close biomarker monitoring to guide timely clinical management.

5. Conclusions and Future Perspectives

Interleukin-6 (IL-6) emerges as a central mediator at the intersection of inflammation, immunity, and disease pathogenesis. Through its pleiotropic signaling, particularly via the IL-6/JAK/STAT3 axis, IL-6 orchestrates biological processes fundamental to both tumor progression and host defense against infection. Its dual role, protective in acute responses yet pathogenic when chronically activated, positions IL-6 as a molecular bridge linking oncogenesis and infection-driven inflammation across the lifespan. This functional versatility underpins its relevance as a diagnostic biomarker, prognostic indicator, and therapeutic target in both oncologic and infectious diseases.
In oncology, elevated IL-6 levels correlate with disease aggressiveness and poor prognosis in both adult and pediatric malignancies, including solid tumors and hematologic cancers. Dysregulated IL-6 signaling contributes to tumor proliferation, angiogenesis, immune evasion, and therapeutic resistance. Therapeutic strategies aimed at blocking IL-6 or its downstream signaling components have shown encouraging preclinical and early clinical results, particularly when combined with immune checkpoint inhibitors or targeted agents, supporting the rationale for IL-6 directed combination approaches.
In infectious diseases, IL-6 serves as a rapid and sensitive biomarker of systemic inflammation, with proven diagnostic and prognostic value in both adults and children. Elevated IL-6 levels can support early infection detection, severity assessment, and outcome prediction. In bacterial infections, IL-6 may aid in distinguishing Gram-negative (GN) from Gram-positive (GP) pathogens, in both adults and immunocompromised pediatric patients. In viral infections, increased elevated IL-6 concentrations have been associated with severe airway inflammation, hyperinflammatory states, and adverse clinical outcomes, underscoring its utility for risk stratification and clinical monitoring.

5.1. Limitations and Clinical Challenges

Despite the substantial body of evidence supporting IL-6 as a clinically relevant biomarker, several limitations currently restrict its routine implementation.
First, there is considerable heterogeneity in IL-6 measurement methodologies, including differences in assay platforms (e.g., flow cytometry, ELISA), analytical sensitivity, sample handling and timing of measurement (in some cases restricted to fever onset), which hampers inter-study comparability.
Second, reported IL-6 values lack standardization, with inconsistent use of means, medians, ranges, or interquartile ranges, often without clear specification of the clinical context (baseline, progression, treatment response).
Third, many studies, particularly in oncology, are observational or retrospective and may be subject to selection and publication bias, potentially overestimating IL-6’s predictive value. Moreover, age-specific reference ranges are largely unavailable, cohort sizes are small, and developmental immune variability further complicates interpretation. As a result, adult-derived thresholds are frequently extrapolated to children, reducing clinical accuracy and translational validity.
Moreover, IL-6 is a non-specific inflammatory marker whose levels can be influenced by comorbidities, infections, treatment-related toxicity, and stress responses, emphasizing the need for cautious interpretation within well-defined clinical frameworks. IL-6 may be most informative when considered in combination with other biomarkers rather than used in isolation. Integrating IL-6 with markers such as CRP, ferritin, or procalcitonin can provide a more comprehensive picture of the inflammatory response, enhancing the ability to predict disease severity and patient outcomes. This multimarker approach allows for better risk stratification and may support more timely and targeted clinical decisions while mitigating the limitations inherent to any single biomarker.
Overcoming these limitations through larger prospective studies with standardized methods, combined with the use of additional biomarkers, will be key to clarifying the role of IL-6 as a biomarker in adult and pediatric cancers as well as infectious diseases.

5.2. Future Perspectives

Future research should prioritize the establishment of age, disease, and context-specific reference ranges, supported by assay harmonization and standardized reporting guidelines. The integration of IL-6 into multimodal biomarker strategies, combining cytokine profiling with genomic, proteomic, and immunologic data, may enhance diagnostic precision and prognostic accuracy while mitigating the limitations of single-marker approaches. In parallel, further investigation into IL-6-targeted combination therapies is warranted to fine-tune inflammatory signaling without compromising host defense, particularly in pediatric and immunocompromised patients.
Ultimately, a deeper and more standardized understanding of IL-6 signaling across oncologic and infectious diseases may transform this cytokine from a versatile biomarker into a cornerstone of precision medicine. By bridging immuno-oncology and infectious disease therapeutics, IL-6 may serve as a valuable tool for personalized risk stratification, therapeutic guidance, and the improvement of clinical outcomes across a wide range of patient populations.

Author Contributions

M.A. and M.A.C. conceptualized, reviewed and edited the manuscript. G.D.B. and C.S. drafted, wrote and edited the manuscript; I.C., O.L. and M.S. reviewed and edited the manuscript. Both G.D.B. and C.S. contributed equally to this manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No primary research result, software, or code has been included, and no new data were generated or analyzed as part of this review. Data sharing is not applicable.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
ANCAbsolute Neutrophil Count
ADAM10A Disintegrin and Metalloproteinase 10
ADAM17A Disintegrin and Metalloproteinase 17
ALLAcute Lymphoblastic Leukemia
AMLAcute Myeloid Leukemia
ARDSAcute Respiratory Distress Syndrome
AUCArea Under the Curve
B-ALLB-cell Acute Lymphoblastic Leukemia
CARChimeric Antigen Receptor
CBACytometric Bead Array
CD126Interleukin-6 Receptor α
CD130Glycoprotein 130
CDK4/6Cyclin-Dependent Kinase 4 and 6
CIConfidence Interval
COVID-19Coronavirus Disease 2019
CRPC-Reactive Protein
CRSCytokine Release Syndrome
ECLIAElectrochemiluminescence Immunoassay
EGFREpidermal Growth Factor Receptor
ELISAEnzyme-Linked Immunosorbent Assay
EMAEuropean Medicines Agency
EMTEpithelial-to-Mesenchymal Transition
EFSEvent-Free Survival
FDAFood and Drug Administration
FluAInfluenza A
GNGram-Negative
GPGram-Positive
HSCsHematopoietic Stem Cells
IL-1Interleukin-1
IL-1βInterleukin-1 beta
IL-6Interleukin-6
IL-6RInterleukin-6 Receptor
IL-10Interleukin-10
IQRInterquartile Range
MAPKMitogen-Activated Protein Kinase
MDIMicrobiologically Proven Infection
mTORMechanistic Target of Rapamycin
NSCLCNon-Small Cell Lung Cancer
PD-1Programmed Cell Death Protein 1
PD-L1Programmed Death-Ligand 1
PCTProcalcitonin
PI3KPhosphoinositide 3-Kinase
RASRat Sarcoma Virus Oncogene
RIARadioimmunoassay
ROCReceiver Operating Characteristic
RRRelative Risk
RSVRespiratory Syncytial Virus
sIL-6RSoluble Interleukin-6 Receptor
STAT3Signal Transducer and Activator of Transcription 3
TAMsTumor-Associated Macrophages
TMETumor Microenvironment
TfhT Follicular Helper Cells
Th17T Helper 17 Cells
TregRegulatory T Cells
TNF-αTumor Necrosis Factor Alpha
JAKJanus Kinase
AKTProtein Kinase B
ERKExtracellular Signal-Regulated Kinase

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Figure 1. Schematic representation of Classical and Trans-Signaling Interleukin-6 pathways. (A) Classical IL-6 signaling involves the binding of IL-6 to membrane-bound IL-6R, which promotes the assembly of a heterohexameric complex consisting of two molecules each of IL-6, IL-6R, and the signal-transducing subunit gp130. This complex triggers JAK/STAT3 pathway activation and drives the transcription of STAT3-dependent target genes. Beyond the JAK/STAT3 axis, the IL-6/IL-6R/gp130 complex can also stimulate the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways [6]. (B) In the IL-6 trans-signaling pathway, IL-6 interacts with the soluble form of IL-6R (sIL-6R), which is generated either through alternative splicing of IL-6R mRNA or by proteolytic cleavage of the membrane-bound receptor mediated by ADAM10 or ADAM17 [7]. The resulting IL-6/sIL-6R complex subsequently binds to gp130, inducing its dimerization and activating downstream signaling cascades analogous to those observed in classical IL-6 signaling.
Figure 1. Schematic representation of Classical and Trans-Signaling Interleukin-6 pathways. (A) Classical IL-6 signaling involves the binding of IL-6 to membrane-bound IL-6R, which promotes the assembly of a heterohexameric complex consisting of two molecules each of IL-6, IL-6R, and the signal-transducing subunit gp130. This complex triggers JAK/STAT3 pathway activation and drives the transcription of STAT3-dependent target genes. Beyond the JAK/STAT3 axis, the IL-6/IL-6R/gp130 complex can also stimulate the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways [6]. (B) In the IL-6 trans-signaling pathway, IL-6 interacts with the soluble form of IL-6R (sIL-6R), which is generated either through alternative splicing of IL-6R mRNA or by proteolytic cleavage of the membrane-bound receptor mediated by ADAM10 or ADAM17 [7]. The resulting IL-6/sIL-6R complex subsequently binds to gp130, inducing its dimerization and activating downstream signaling cascades analogous to those observed in classical IL-6 signaling.
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Figure 2. Pleiotropic Roles of Interleukin-6 in Immune Regulation, Hematopoiesis, and Tissue Homeostasis. Interleukin-6 (IL-6) displays broad pleiotropic activity on immune, hematopoietic, and stromal cells, emphasizing its fundamental role in coordinating immune activation, hematopoietic processes, and tissue homeostasis. In B cells, IL-6 drives differentiation into plasma cells and enhances immunoglobulin production. In T cells, it promotes Th17 differentiation, inhibits Treg development, and supports T follicular helper (Tfh) cell function. In megakaryocytes, IL-6 stimulates maturation and platelet production, while in hepatocytes it induces acute-phase protein synthesis and modulates metabolic and inflammatory responses. In hematopoietic stem cells (HSCs), IL-6 promotes proliferation, survival, and multilineage differentiation, particularly under stress or inflammatory conditions. In osteoclasts, it enhances differentiation and bone resorption, contributing to bone remodeling and pathological bone loss. In myeloma, mesangial, and keratinocyte cells, IL-6 functions as a growth and survival factor, stimulating cell proliferation, the release of inflammatory mediators, and tissue repair processes. Collectively, these actions highlight IL-6 as a central mediator linking immune activation, hematopoiesis, and tissue homeostasis.
Figure 2. Pleiotropic Roles of Interleukin-6 in Immune Regulation, Hematopoiesis, and Tissue Homeostasis. Interleukin-6 (IL-6) displays broad pleiotropic activity on immune, hematopoietic, and stromal cells, emphasizing its fundamental role in coordinating immune activation, hematopoietic processes, and tissue homeostasis. In B cells, IL-6 drives differentiation into plasma cells and enhances immunoglobulin production. In T cells, it promotes Th17 differentiation, inhibits Treg development, and supports T follicular helper (Tfh) cell function. In megakaryocytes, IL-6 stimulates maturation and platelet production, while in hepatocytes it induces acute-phase protein synthesis and modulates metabolic and inflammatory responses. In hematopoietic stem cells (HSCs), IL-6 promotes proliferation, survival, and multilineage differentiation, particularly under stress or inflammatory conditions. In osteoclasts, it enhances differentiation and bone resorption, contributing to bone remodeling and pathological bone loss. In myeloma, mesangial, and keratinocyte cells, IL-6 functions as a growth and survival factor, stimulating cell proliferation, the release of inflammatory mediators, and tissue repair processes. Collectively, these actions highlight IL-6 as a central mediator linking immune activation, hematopoiesis, and tissue homeostasis.
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Table 2. Role of IL-6 in Pediatric Cancers.
Table 2. Role of IL-6 in Pediatric Cancers.
Pediatric CancerRole of IL-6IL-6 Levels
(pg/mL)		Assay
Method		Clinical
Implications		References
NeuroblastomaMarker of high-risk disease and poor prognosisPeripheral blood: High-risk: ~23.9; low/intermediate: ~4.3; controls: ~3.3
Bone marrow: High-risk: ~15 pg/mL, undetectable in low/intermediate		ELISAPrognostic marker of high-risk disease[58]
OsteosarcomaTumor progression and metastasisElevated vs. controlsELISAAssociated with lung metastasis and poor survival[59]
Acute
lymphoblastic leukemia (ALL)		Modulates immune signaling; context-dependentVariable
(neonatal samples)		Multiplex immunoassayPotential early-life biomarker; may indicate increased ALL risk[20]
Acute myeloid leukemia
(AML)		Microenvironment-mediated chemoresistanceElevated at diagnosis in poor EFSMultiplex
bead-based assay		Prognostic marker;
relapse risk		[21]
Table 3. Role of IL-6 in Bacterial Infections in Adult and Pediatric Patients.
Table 3. Role of IL-6 in Bacterial Infections in Adult and Pediatric Patients.
Patient GroupClinical ContextRole of IL-6IL-6 Levels (pg/mL)Clinical
Implications		References
Adult patientsBloodstream infection (BSI)Marker of systemic inflammation and septic shock<534.7 excludes septic shock; >1000 associated with septic shock and mortalityRisk stratification and early identification of septic shock[67]
Bloodstream infection (BSI)Differentiation between Gram-negative (GN) and Gram-positive infections (GP)GN-BSI: 4–31-fold higher than GP-BSIMay guide early pathogen-oriented antimicrobial therapy[67]
Bloodstream infection (BSI)Discrimination between Gram-negative and Gram-positive infectionsGN-BSI: median 397.4 (IQR 125.1–1447.0); GP-BSI: 172.4 (IQR 84.81–216.1)Diagnostic aid for Gram-negative infection and severity assessment[68]
Pediatric cancer patientsFebrile neutropeniaEarly marker of Gram-negative infectionGram-negative bacteremia: median 166 (21–1780); Gram-positive bacteremia: 26 (16–33)Early identification of fever infectious vs. non-infectious febrile episodes[70]
Febrile neutropeniaPredictor of Gram-negative bacteremiaGN infection: median 169 (IQR 124–2600); sterile: 52; Gram-positive infection: 17.5Guides early escalation of antimicrobial therapy[72]
Febrile neutropeniaIndependent predictor of Gram-negative bacteremia≥185 predictive of GN-BSI (AUC 0.77)Risk stratification and early clinical decision-making[71]
Table 4. The Role of IL-6 in Viral Infections in Adult and Pediatric Patients.
Table 4. The Role of IL-6 in Viral Infections in Adult and Pediatric Patients.
Infection ContextRole of IL-6IL-6
Levels		Clinical
Implications		Reference
Viral infections (Influenza A, RSV, COVID-19) in adultsReflects systemic inflammation and immune activation.Elevated level of IL-6 in all viral infections (AUC > 0.85); Elevated levels of IL-6 in FluA non-survivors (AUC = 0.80) compared to FluA survivors.Diagnostic biomarker to identify viral infections; elevated levels associated with worse outcomes, complications, prolonged hospitalization and higher risk of mortality.[75]
Influenza A(H1N1)pdm09 infection in adultsIndicator of hyperinflammatory response and predictor of mortality and disease severity.Higher levels of IL-6 in early stage of lethal cases (mean ± SE, 812 pg/mL ± 451.3, p < 0.001) and in surviving critically ill patients (mean ± SE, 112.6 pg/mL ± 53, p < 0.05) compared to healthy individuals (mean ± SE, 5.039 pg/mL ± 1.69) and non-severe recovered cases (mean ± SE, 6.11 pg/mL ± 3.57).Predictive biomarker for identifying patients at higher risk of fatal outcomes.[77]
H1N1 influenza in childrenIL-6 contributes to airway inflammation, respiratory dysfunction and disease severity.Significantly elevated IL-6 levels (108.1 ± 22.8 pg/mL) in H1N1-infected children.Biomarker for early detection of severe airway inflammation in pediatric H1N1 infection.[79]
Severe influenza with febrile seizures in childrenServes as a risk factor for febrile seizures, reflecting systemic and neuronal inflammation.IL-6 ≥ 9.84 pg/mL associated with higher risk of developing febrile seizures.IL-6 levels can help identify children at risk of febrile convulsions, guiding early clinical monitoring and treatment optimization.[80]
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Benedetto, G.D.; Sorice, C.; Cantiello, I.; Savarese, M.; Leone, O.; Capozza, M.A.; Alfieri, M. Interleukin-6: A Central Biomarker in Adult and Pediatric Cancer and Infectious Disease. Biologics 2026, 6, 5. https://doi.org/10.3390/biologics6010005

AMA Style

Benedetto GD, Sorice C, Cantiello I, Savarese M, Leone O, Capozza MA, Alfieri M. Interleukin-6: A Central Biomarker in Adult and Pediatric Cancer and Infectious Disease. Biologics. 2026; 6(1):5. https://doi.org/10.3390/biologics6010005

Chicago/Turabian Style

Benedetto, Giorgia Di, Carmen Sorice, Immacolata Cantiello, Maria Savarese, Ornella Leone, Michele Antonio Capozza, and Mariaevelina Alfieri. 2026. "Interleukin-6: A Central Biomarker in Adult and Pediatric Cancer and Infectious Disease" Biologics 6, no. 1: 5. https://doi.org/10.3390/biologics6010005

APA Style

Benedetto, G. D., Sorice, C., Cantiello, I., Savarese, M., Leone, O., Capozza, M. A., & Alfieri, M. (2026). Interleukin-6: A Central Biomarker in Adult and Pediatric Cancer and Infectious Disease. Biologics, 6(1), 5. https://doi.org/10.3390/biologics6010005

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