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The Role of Inflammatory Cytokines (Interleukins Family) in Human Disease
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The Role of Inflammatory Cytokines (Interleukins Family) in Human Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 8014

Special Issue Editor

Dr. Diego Fresegna

E-Mail Website
Guest Editor
IRCCS San Raffaele Pisana, Rome, Italy
Interests: neurodegenerative disease; autoimmunity; inflammation; cytokines

Special Issue Information

Dear Colleagues,

In contemporary medical discourse, the profound influence of inflammatory cytokines, particularly those within the interleukin family, on human diseases has become a focal point of investigation. Interleukins, as integral signaling molecules in the immune system, intricately contribute to maintaining the delicate equilibrium between health and disease. The dysregulation of interleukin activity is implicated in a myriad of human disorders. While these cytokines play a pivotal role in orchestrating immune responses, their imbalanced levels or malfunction can instigate detrimental effects. Autoimmune diseases exemplify instances where the immune system’s misguided assault on the body’s own tissues is often linked to the overproduction or misbehavior of specific interleukins. Moreover, the intricate involvement of aberrant interleukin signaling in inflammatory bowel diseases and certain cancers underscores the far-reaching consequences of these molecular interactions. Comprehending the nuanced roles of interleukins in the initiation and progression of human diseases not only enhances our understanding but also opens avenues for targeted therapeutic interventions. As researchers delve deeper into the complexities of these molecular pathways, the prospect of developing precise treatments that modulate interleukin activity holds significant promise. This points towards a future where personalized medicine revolutionizes the healthcare landscape, offering tailored solutions for improved patient outcomes.

Dr. Diego Fresegna
Guest Editor

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Keywords

  • cytokine signaling
  • immunotherapy
  • immune modulation
  • precision medicine
  • disease pathogenesis
  • immunological disorders
  • therapeutic targets
  • inflammation biomarkers
  • immunomodulatory drugs
  • cellular immune response

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Published Papers (5 papers)

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Research

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16 pages, 25310 KiB  
Article
Interleukin-1β Inhibits Ovarian Cancer Cell Proliferation and Metastasis Through the MAPK/MMP12 Pathway
by Zhenling Ma, Jiajia Zhang, Zhenzhen Li, Yiyang Zhu, Xulu Han, Lanxiang Lei, Kun Cheng and Wei Liu
Int. J. Mol. Sci. 2025, 26(7), 3287; https://doi.org/10.3390/ijms26073287 - 1 Apr 2025
Viewed by 466
Abstract
Epithelial ovarian cancer (EOC) is a gynecological tumor with high mortality. Despite aggressive treatment, survival rates for patients with advanced EOC are low, and more effective methods of diagnosis and treatment are urgently needed. Inflammation and cancer are strongly associated; however, the mechanisms [...] Read more.
Epithelial ovarian cancer (EOC) is a gynecological tumor with high mortality. Despite aggressive treatment, survival rates for patients with advanced EOC are low, and more effective methods of diagnosis and treatment are urgently needed. Inflammation and cancer are strongly associated; however, the mechanisms that mediate this relationship are not fully understood. In this study, we found that the expression of interleukin-1β (IL-1β), a proinflammatory cytokine, increased in an ovarian cancer tissue microarray (TMA) and inhibited A2780 and SKOV3 cell viability and metastasis. Recombinant IL-1β protein and the overexpression of IL-1β decreased the proliferation and metastasis of ovarian cancer cells. IL-1β deficiency promoted proliferation and metastasis. Moreover, transcriptome sequencing revealed that IL-1β downregulates the expression of matrix metalloproteinase 12 (MMP12). The signaling pathway involving MAPK/AP-1/MMP12 is involved in IL-1β-regulated ovarian cancer progression. Overall, we found that the proinflammatory cytokine IL-1β inhibits ovarian cancer cell viability and metastasis. These findings provided deeper insights into inflammation and cancer progression. Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines (Interleukins Family) in Human Disease)
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9 pages, 236 KiB  
Article
Changes in Levels of Serum Cytokines and Chemokines in Perforated Appendicitis in Children
by Wen-Ya Lin, En-Pei Lee, Chun-Yu Chen, Bei-Cyuan Guo, Mao-Jen Lin and Han-Ping Wu
Int. J. Mol. Sci. 2024, 25(11), 6076; https://doi.org/10.3390/ijms25116076 - 31 May 2024
Cited by 1 | Viewed by 964
Abstract
Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with [...] Read more.
Appendicitis is primarily diagnosed based on intraoperative or histopathological findings, and few studies have explored pre-operative markers of a perforated appendix. This study aimed to identify systemic biomarkers to predict pediatric appendicitis at various time points. The study group comprised pediatric patients with clinically suspected appendicitis between 2016 and 2019. Pre-surgical serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), intercellular cell-adhesion molecule-1 (ICAM-1), and endothelial selectin (E-selectin) levels were tested from day 1 to day 3 of the disease course. The biomarker values were analyzed and compared between children with normal appendices and appendicitis and those with perforated appendicitis (PA) and non-perforated appendicitis. Among 226 pediatric patients, 106 had non-perforated appendicitis, 102 had PA, and 18 had normal appendices. The levels of all serum proinflammatory biomarkers were elevated in children with acute appendicitis compared with those in children with normal appendices. In addition, the serum IL-6 and TNF-α levels in children with PA were significantly higher, with an elevation in TNF-α levels from days 1 and 2. In addition, serum IL-6 levels increased significantly from days 2 and 3 (both p < 0.05). Serum ICAM-1 and E-selectin levels were elevated in the PA group, with consistently elevated levels within the first three days of admission (all p < 0.05). These results indicate that increased serum levels of proinflammatory biomarkers including IL-6, TNF-α, ICAM-1, and E-selectin could be used as parameters in the prediction and early diagnosis of acute appendicitis, especially in children with PA. Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines (Interleukins Family) in Human Disease)
18 pages, 3343 KiB  
Article
Targeting NF-κB Signaling: Selected Small Molecules Downregulate Pro-Inflammatory Cytokines in Both Food Allergen and LPS-Induced Inflammation
by Milena Zlatanova, Andrijana Nešić, Jovana Trbojević-Ivić, Danilo Četić and Marija Gavrović-Jankulović
Int. J. Mol. Sci. 2024, 25(11), 5798; https://doi.org/10.3390/ijms25115798 - 26 May 2024
Cited by 1 | Viewed by 2176
Abstract
Although inflammation is primarily a protective response guarding the human body, it can result in a variety of chronic diseases such as allergies, auto-immune, cardiovascular diseases, and cancer. In NF-κB-mediated inflammation, many small molecules and food compounds characterized as nutraceuticals have shown positive [...] Read more.
Although inflammation is primarily a protective response guarding the human body, it can result in a variety of chronic diseases such as allergies, auto-immune, cardiovascular diseases, and cancer. In NF-κB-mediated inflammation, many small molecules and food compounds characterized as nutraceuticals have shown positive effects associated with immunomodulatory properties. We investigated the effects of selected bioactive small molecules, commonly found in food components, vanillyl alcohol (VA) and lauric acid (LA), on different cell lines exposed to pro-inflammatory stimuli, lipopolysaccharide (LPS), and the food allergen actinidin (Act d 1). Pro-inflammatory cytokines were downregulated in response to both VA and LA, and this downregulation was caused by a decrease in the activation of the NF-κB pathway and the translocation of p65, the pathway’s major component. Small nutraceutical molecules, VA and LA, showed not only inhibition of the pro-inflammatory cytokines, but also inhibition of the NF-κB activation, and reduced translocation of the p65 component. The present study may contribute to the therapeutic use of these molecules for various inflammatory diseases, which have in common an increased expression of pro-inflammatory cytokines and NF-κB-mediated inflammation. Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines (Interleukins Family) in Human Disease)
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Review

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23 pages, 1549 KiB  
Review
Meteorin-β: A Novel Biomarker and Therapeutic Target on Its Way to the Regulation of Human Diseases
by Bei Wang, Xiao Li and Xun Gao
Int. J. Mol. Sci. 2025, 26(10), 4485; https://doi.org/10.3390/ijms26104485 - 8 May 2025
Viewed by 132
Abstract
The novel secreted protein Meteorin-β (Metrnβ) is a homologous protein of the neurotrophic regulator Meteorin, which is widely expressed in the skin, mucous membranes, and white adipose tissue upon stimulation by a variety of inflammatory mediators, including cytokines and chemokines, while, at the [...] Read more.
The novel secreted protein Meteorin-β (Metrnβ) is a homologous protein of the neurotrophic regulator Meteorin, which is widely expressed in the skin, mucous membranes, and white adipose tissue upon stimulation by a variety of inflammatory mediators, including cytokines and chemokines, while, at the same time Metrnβ may also regulate the expression of these cytokines and chemokines. As a small secreted protein with low tissue specificity, Metrnβ plays vital roles in energy metabolism, insulin sensitivity regulation, neurodevelopment, white fat browning, and inflammatory response. Specifically, Metrnβ may act as an adipokine, myokine, neurotrophic factor, and cytokine, thereby being involved in the pathological and physiological processes of various human diseases, including metabolic, autoimmune and infectious/allergic diseases, and certain types of tumors. This review aims to systematically introduce the current research progress on Metrnβ, including its expression and distribution profiles, biological functions, and immunomodulatory roles in the process of human diseases. Additionally, we also discuss its potential as a biomarker, as well as a therapeutic/preventive agent for human diseases. Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines (Interleukins Family) in Human Disease)
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14 pages, 1156 KiB  
Review
Inflammatory Biomarkers and Gait Impairment in Older Adults: A Systematic Review
by Lorenzo Brognara, Oscar Caballero Luna, Francesco Traina and Omar Cauli
Int. J. Mol. Sci. 2024, 25(3), 1368; https://doi.org/10.3390/ijms25031368 - 23 Jan 2024
Cited by 11 | Viewed by 2688
Abstract
Peripheral inflammation and gait speed alterations are common in several neurological disorders and in the aging process, but the association between the two is not well established. The aim of this systematic literary review is to determine whether proinflammatory markers are a positive [...] Read more.
Peripheral inflammation and gait speed alterations are common in several neurological disorders and in the aging process, but the association between the two is not well established. The aim of this systematic literary review is to determine whether proinflammatory markers are a positive predictor for gait impairments and their complications, such as falls in older adults, and may represent a risk factor for slow gait speed and its complications. The systematic review was performed in line with the Preferred Report Items for Systematic Review and Meta-Analyses (PRISMA). A protocol for literature searches was structured a priori and designed according to the International Perspective Register of Systemic Review (PROSPERO: CRD42023451108). Peer-reviewed original articles were identified by searching seven electronic databases: Excerpta Medica Database (EMBASE), SciVerse (ScienceDirect), Scopus, PubMed, Medline, Web of Science, and the Cochrane Library. The search strategy was formulated based on a combination of controlled descriptors and/or keywords related to the topic and a manual search was conducted of the reference lists from the initially selected studies to identify other eligible studies. The studies were thoroughly screened using the following inclusion criteria: older adults, spatiotemporal gait characteristics, and proinflammatory markers. A meta-analysis was not performed due to the heterogeneity of the studies, and the results were narratively synthesized. Due to the clinical and methodological heterogeneity, the studies were combined in a narrative synthesis, grouped by the type of biomarkers evaluated. A standardized data extraction form was used to collect the following methodological outcome variables from each of the included studies: author, year, population, age, sample size, spatiotemporal gait parameters such as gait velocity, and proinflammatory markers such as TNF-α, high sensitivity C-reactive (CRP) proteins, and IL-6. We included 21 out of 51 studies in our review, which examined the association between inflammatory biomarkers and gait impairment. This review highlights the role of TNF-α, CRP, and IL-6 in gait impairment. Biomarkers play an important role in the decision-making process, and IL-6 can be an effective biomarker in establishing the diagnosis of slow gait speed. Further longitudinal research is needed to establish the use of molecular biomarkers in monitoring gait impairment. Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines (Interleukins Family) in Human Disease)
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