Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

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 December 2025) | Viewed by 9759

Share This Special Issue

Special Issue Editor

Dr. Juliann G. Kiang

E-Mail Website
Guest Editor

Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889-5648, USA
Interests: signal transduction; apoptosis; autophagy; cytokine/inflammation storm; acute radiation syndrome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the past few years, research on pro-inflammatory and anti-inflammatory cytokines has tremendously furthered our understanding in the field of biology on a molecular level with disease progression. The balance between pro-inflammatory and anti-inflammatory cytokines contributes to homeostasis and maintenance of well-being. This has led to the potential new therapies, providing prophylactic or mitigative benefits to the treatment of complicated diseases. For example, using exosomes packed with cytokine(s) to correct certain metabolic problems or organ dysfunction has been published. A great deal of this progress is due to efforts that bridge across disciplines including molecular biology, biochemistry, pharmacology, and clinical medicine. The focus of this Special Issue is to bring together the most recent developments and state-of-the-art research studies to understand the molecular interaction between pro-inflammatory and anti-inflammatory cytokines and develop advanced prophylactics, mitigators, and therapies by managing the crosstalk of pro-inflammatory and anti-inflammatory cytokines. Original research articles, comprehensive reviews, and other article types are all welcome.

Suitable topics include, but are not limited to, the following:

Cell-based therapy;
Nanomedicine;
Drug development and mechanisms of drug action;
Innate and acquired immunity;
Microbe–host response.

Dr. Juliann G. Kiang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

pro-inflammation cytokine
anti-inflammation cytokine
chemotherapy
radiotherapy
signal transduction
microbiome–host response
sepsis
bone marrow
GI
brain

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

22 pages, 7527 KB

Open AccessArticle

Cytokine Profiling for the Prediction of Lethality and High-Dose Exposure in a Murine Partial Body Irradiation Model

by Wanchang Cui, Lisa Hull, Asher Rothstein, Li Wang, Bin Lin, Min Zhai, Alia Weaver and Mang Xiao

Int. J. Mol. Sci. 2026, 27(7), 3213; https://doi.org/10.3390/ijms27073213 - 1 Apr 2026

Viewed by 608

Abstract

Accurate radiation biodosimetry is urgently needed for medical management after large-scale radiation exposure. Partial-body irradiation with 5% bone marrow sparing (PBI/BM5) provides a realistic radiation model. The current study specifically focused on the high-dose lethality window (12–16 Gy), where survival transitioned from 100% to 0%, representing a clinically distinct and underserved scenario requiring dedicated biodosimetry tools. We defined the survival profile of male C57BL/6 mice after PBI/BM5 and found that doses of 13.5–14.0 Gy were nonlethal within 12 days, whereas 15.0–15.5 Gy caused 100% mortality within 12 days, with a calculated LD_50/12 of 14.68 Gy. A separate cohort of 14.0 Gy showed 100% survival up to 90 days post-radiation. To develop serum cytokine-based biodosimetry in high-dose radiation exposure, mice were exposed to 12.0–16.0 Gy PBI/BM5, and serum was collected on days 1, 3, and 7. A multiplex cytokine assay was used to quantify 70 total cytokines/chemokines. After the exclusion of 4 targets outside detection limits, 66 markers were utilized for downstream analysis. PCA, clustering and heatmaps, and LASSO classification revealed that cytokine signatures can classify radiation groups/status/doses. A 4-cytokine panel (IL-7, GDF-15, IL-16 and FLT3L) could distinguish naïve vs. irradiated mice on all study days. A 24-cytokine signature panel distinguished radiation survivors vs. non-survivors, and another 34-cytokine panel separated radiation doses (12–16 Gy); the prediction was better on day 7 compared to earlier time points. This exploratory study was specifically designed to define the systemic inflammatory response in a high-dose window where survival transitions from 100% to 0% (the ‘lethality threshold’) in a clinically relevant partial-body irradiation model. These findings show that serum cytokines have strong potential for high-dose triage, survival prediction, and dose discrimination within the near-lethal exposure range in a clinically relevant PBI/BM5 model. Extension to lower dose ranges is an important direction for future work. Full article

(This article belongs to the Special Issue Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines)

► Show Figures

Figure 1

22 pages, 5855 KB

Open AccessArticle

JNJ-26366821 Attenuates Radiation-Induced Pro-Inflammatory Cytokines and miRNAs and Triggers TR/RXR Signaling Pathway

by Vidya P. Kumar, Bernedette Hritzo, Dharmendra Kumar Soni, Venkateshwara Rao Dronamraju, Gregory P. Holmes-Hampton, Roopa Biswas and Sanchita P. Ghosh

Int. J. Mol. Sci. 2026, 27(5), 2181; https://doi.org/10.3390/ijms27052181 - 26 Feb 2026

Viewed by 469

Abstract

JNJ-26366821, a novel thrombopoietin mimetic peptide (TPOm), is shown to increase platelets (PLTs) transiently in peripheral blood. We hypothesized that increases in PLT counts may involve stimulation of hematopoiesis via induction of cytokines, growth factors, and microRNAs. Hence, we measured various cytokines, chemokines, and growth factors in serum. Time-course analysis of G-CSF, IL-5, IL-6, IL-9, IL-10, TNFα, IL-1α, and IL-1β expression was significantly altered in the control group at 9.5 Gy compared to a lower non-lethal dose of 7 Gy on days 7 to 15 post-exposure. TPOm pre-treatment significantly ameliorated the changes in expression of these pro-inflammatory cytokines and growth factors. Additionally, we show that TPOm differentially modulates the miRNA expression profiles in the spleen of irradiated mice compared to controls at both early times as well as later times after irradiation. These results suggest a possible role of TPOm in protecting animals from radiation-induced thrombocytopenia and lethality by attenuating radiation-induced inflammatory cytokines and miRNAs. Full article

(This article belongs to the Special Issue Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines)

► Show Figures

Graphical abstract

13 pages, 2577 KB

Open AccessArticle

Anti-IL-4, Anti-IL-17, and Anti-IFN-Gamma Activity in the Saliva of Amblyomma sculptum Ticks

by Helioswilton Sales-Campos, Chamberttan Souza Desidério, Rafael Obata Trevisan, Rodolfo Pessato Timóteo, Victor Hugo Palhares Flávio-Reis, Yago Marcos Pessoa-Gonçalves, Marcos Vinicius da Silva, Eliane Esteves, Thiago de Jesus Oliveira, Pedro Ismael da Silva Junior and Carlo José Freire Oliveira

Int. J. Mol. Sci. 2025, 26(10), 4734; https://doi.org/10.3390/ijms26104734 - 15 May 2025

Cited by 2 | Viewed by 1279

Abstract

The saliva of hematophagous arthropods, such as ticks and triatomines, contains bioactive ligands capable of modulating immune molecules, including cytokines. Cytokines play a critical role in immune regulation and have therapeutic relevance in inflammatory and immune-mediated diseases. Despite recent advances, identifying cytokine-binding molecules remains a significant challenge. Interferon-gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-17 (IL-17) are key cytokines involved in inflammation, adaptive immunity, and host defense. This study evaluated the ability of salivary components from Amblyomma sculptum and compared the results to the triatomine Rhodnius neglectus (used as control) to bind to IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α using ELISA assays with human cytokines. Saliva samples were tested at dilutions of 1:25, 1:50, and 1:100. Saliva from A. sculptum, which demonstrated significant anti-cytokine activity, was fractionated via HPLC to identify the active components. The results confirmed the inhibitory capacity of A. sculptum saliva on IFN-γ, IL-4, and IL-17, with inhibition rates ranging from 30% to 70%, depending on the cytokine and dilution. No inhibitory activity was observed against IL-2, IL-6, IL-10, or TNF-α. These findings underscore the immunomodulatory role of A. sculptum saliva during tick feeding and suggest its potential for the development of novel immunobiologics to treat inflammatory and immune-mediated diseases. Full article

(This article belongs to the Special Issue Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines)

► Show Figures

Figure 1

14 pages, 2444 KB

Open AccessArticle

RIPK2 Is Crucial for the Microglial Inflammatory Response to Bacterial Muramyl Dipeptide but Not to Lipopolysaccharide

by Changjun Yang, Maria Carolina Machado da Silva, John Aaron Howell, Jonathan Larochelle, Lei Liu, Rachel E. Gunraj, Antônio Carlos Pinheiro de Oliveira and Eduardo Candelario-Jalil

Int. J. Mol. Sci. 2024, 25(21), 11754; https://doi.org/10.3390/ijms252111754 - 1 Nov 2024

Cited by 4 | Viewed by 3152

Abstract

Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is a kinase that is essential in modulating innate and adaptive immune responses. As a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs), it is implicated in the signaling triggered by recognition of microbe-associated molecular patterns by NOD1/2 and TLRs. Upon activation of these innate immune receptors, RIPK2 mediates the release of pro-inflammatory factors by activating mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB). However, whether RIPK2 is essential for downstream inflammatory signaling following the activation of NOD1/2, TLRs, or both remains controversial. In this study, we examined the role of RIPK2 in NOD2- and TLR4-dependent signaling cascades following stimulation of microglial cells with bacterial muramyl dipeptide (MDP), a NOD2 agonist, or lipopolysaccharide (LPS), a TLR4 agonist. We utilized a highly specific proteolysis targeting chimera (PROTAC) molecule, GSK3728857A, and found dramatic degradation of RIPK2 in a concentration- and time-dependent manner. Importantly, the PROTAC completely abolished MDP-induced increases in iNOS and COX-2 protein levels and pro-inflammatory gene transcription of Nos2, Ptgs2, Il-1β, Tnfα, Il6, Ccl2, and Mmp9. However, increases in iNOS and COX-2 proteins and pro-inflammatory gene transcription induced by the TLR4 agonist, LPS, were only slightly attenuated with the GSK3728857A pretreatment. Further findings revealed that the RIPK2 PROTAC completely blocked the phosphorylation and activation of p65 NF-κB and p38 MAPK induced by MDP, but it had no effects on the phosphorylation of these two mediators triggered by LPS. Collectively, our findings strongly suggest that RIPK2 plays an essential role in the inflammatory responses of microglia to bacterial MDP but not to LPS. Full article

(This article belongs to the Special Issue Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 1374 KB

Open AccessReview

The Pleiotropic Effect of Complement C5a-C5aR1 Pathway in Diseases: From Immune Regulation to Targeted Therapy

by Baohong Xu, Zhi Zhou, Yang Xiao, Qiaolin Liu, Tiaoyi Xiao, Zhao Lv and Hongquan Wang

Int. J. Mol. Sci. 2025, 26(23), 11693; https://doi.org/10.3390/ijms262311693 - 3 Dec 2025

Viewed by 1831

Abstract

The complement system plays a pivotal role in the body’s immune defense mechanism. Its key effector molecule C5a and its primary receptor C5aR1 exhibit complex “double-edged sword” effects in various disease processes, including infectious diseases, inflammatory conditions, tumors, and metabolic disorders. Under normal physiological conditions, moderate levels of C5a bind to the C5aR1 receptor, recruiting immune cells to the site of infection to participate in immune defense and enhancing the body’s ability to clear pathogens. However, in various disease states, the C5a-C5aR1 pathway primarily shapes the disease microenvironment through regulating cellular pro-inflammatory and immune functions, angiogenesis processes, and tissue repair processes. It also promotes tumor immune escape through a novel mechanism through modulating the polarization of myeloid-derived suppressor cells (MDSCs) and regulating T cell function. The C5a-mediated “inflammation–fibrosis–metabolic reprogramming” vicious cycle has become a key molecular basis driving disease progression, maintaining pathological states, and promoting abnormal tissue damage repair in chronic inflammatory diseases. Through elucidating the structural biology of C5aR1 and designing allosteric modulators, nanobodies, and bifunctional molecules as new targeted intervention strategies, we aim to accelerate research progress in related medical fields. This article reviewed the molecular mechanisms of the complement system in tumor immune escape, chronic inflammation, fibrosis, and cardiovascular diseases, and explored the translational potential of targeted interventions. These discussions provide a solid theoretical foundation and new research perspectives for the medical field, aiding in the advancement of further discoveries. Full article

(This article belongs to the Special Issue Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines)

► Show Figures

Figure 1

18 pages, 540 KB

Open AccessReview

An Update on Dynamic Changes in Cytokine Expression and Dysbiosis Due to Radiation Combined Injury

by Juliann G. Kiang and Georgetta Cannon

Int. J. Mol. Sci. 2025, 26(21), 10456; https://doi.org/10.3390/ijms262110456 - 28 Oct 2025

Cited by 1 | Viewed by 1416

Abstract

The complexity of adverse responses from radiation injury (RI) followed by physical trauma, namely, radiation combined injury (RCI), is unique and more pronounced than either insult alone due to a poor understanding of the integration of these insults at the molecular/cellular/tissue and/or organ levels. It was shown that mice receiving ⁶⁰Co γ-photon RCI with wounding had a lower LD_50/30 than RI alone. This survival synergism was observed in bone marrow and the gastrointestinal system, as evidenced by an increase in γ-H2AX expression in bone marrow cell DNA, loss of circulatory blood cells, elevation of serum cytokine concentration, and activation of nuclear factor-κB/inducible nitric oxide synthase, and an earlier onset of bacterial infection and sepsis after RCI than after RI was detected. Dysbiosis (imbalance of the gut microbiota) was observed. There remains a pressing need for both prophylactic countermeasures and therapeutic remedies to deal with RCI threats. Investigations of how RCI can affect this important network of communication between the gut microbiota and other organs, including the brain, lung, heart, liver, kidney, and skin, could lead to new and critical interventions and prevention strategies. This review provides an update on new RCI animal models, dynamic changes in cytokine expression, dysbiosis, as well as links between the gut microbiome and other organs after RCI. Full article

(This article belongs to the Special Issue Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines)

► Show Figures

Journal Menu

Journal Browser

Advances in Pro-Inflammatory and Anti-Inflammatory Cytokines

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (6 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI