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Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0
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Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0

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: 20 February 2025 | Viewed by 10688

Special Issue Editors

Prof. Dr. Anna Cieslinska

E-Mail Website
Guest Editor
Department of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
Interests: genetics; biochemistry; biotechnology; molecular biology; diets; SNPs; mutations; opioids; proteins
Special Issues, Collections and Topics in MDPI journals
Dr. Edyta Sienkiewicz-Szłapka

E-Mail Website
Guest Editor
Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
Interests: biochemistry; opioid peptides; food proteins; vitamins; nutrition; allergy; autoimmune; neurodevelopmental diseases; nutrigenomics; nutricosmetics; cosmeceuticals; dermocosmetics

Special Issue Information

Dear Colleagues,

Cytokines are crucial in modulating the immune system, and as key modulators of inflammation, are produced in response to infection. Proinflammatory cytokines are positive mediators of inflammation, and anti-inflammatory cytokines are immunoregulatory molecules that control the pro-inflammatory cytokine response. Certain cytokines are involved in not only the initiation but also the progression/regression of diseases.

In this Special Issue of the International Journal of Molecular Sciences, we aim to focus on the latest discoveries and developments in pro-inflammatory and anti-inflammatory interleukins, their relation with diseases in animals and human studies, and the possible underlying mechanisms, thereby supplementing the existing literature on this field. Therefore, we cordially invite scholars from basic, immunological, pathophysiological, nutritional and metabolism research or other related disciplines to submit their original articles, reviews, communications, as well as conceptual papers to this Special Issue.

Prof. Dr. Anna Cieślińska
Dr. Edyta Sienkiewicz-Szłapka
Guest Editors

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 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • cytokines
  • inflammation
  • interleukins
  • IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-17, IL-18, IL-22, IL-37, IL-38, IFN-α, IFN-β, IFN-γ, TGF-β, TNF-α, TNF-β
  • allergy
  • TNF-α
  • chemokines
  • interferon
  • gut inflammation
  • systemic inflammation
  • infection

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Published Papers (6 papers)

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Research

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17 pages, 4221 KiB  
Article
Prognostic Impact of Acute and Chronic Inflammatory Interleukin Signatures in the Tumor Microenvironment of Early Breast Cancer
by Anne-Sophie Heimes, Ina Shehaj, Katrin Almstedt, Slavomir Krajnak, Roxana Schwab, Kathrin Stewen, Antje Lebrecht, Walburgis Brenner, Annette Hasenburg and Marcus Schmidt
Int. J. Mol. Sci. 2024, 25(20), 11114; https://doi.org/10.3390/ijms252011114 - 16 Oct 2024
Viewed by 844
Abstract
Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based [...] Read more.
Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and CXCL1) for metastasis-free survival (MFS) using Kaplan–Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman–Rho correlation coefficient. Kaplan–Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype (p = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290–0.741; p = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; p < 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; p < 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune–inflammatory axis. Full article
(This article belongs to the Special Issue Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0)
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24 pages, 4323 KiB  
Article
Long-Term Oral Administration of Hyperimmune Egg-Based IgY-Rich Formulations Induces Mucosal Immune Response and Systemic Increases of Cytokines Involved in Th2- and Th17-Type Immune Responses in C57BL/6 Mice
by Valentin Nastasa, Bogdan Minea, Aurelian-Sorin Pasca, Andra-Cristina Bostanaru-Iliescu, Alina-Elena Stefan, Daniela Gologan, Robert Capota, Liliana-Georgeta Foia and Mihai Mares
Int. J. Mol. Sci. 2024, 25(16), 8701; https://doi.org/10.3390/ijms25168701 - 9 Aug 2024
Viewed by 3586
Abstract
Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations [...] Read more.
Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response. Full article
(This article belongs to the Special Issue Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0)
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15 pages, 1418 KiB  
Article
Systemic Inflammatory Changes in Spinal Cord Injured Patients after Adding Aquatic Therapy to Standard Physiotherapy Treatment
by María. Teresa Agulló-Ortuño, Helena Romay-Barrero, Johan Lambeck, Juan M. Blanco-Calonge, Rubén Arroyo-Fernández, Paula Richley Geigle, Raquel Menchero, Gonzalo Melgar del Corral and Inés Martínez-Galán
Int. J. Mol. Sci. 2024, 25(14), 7961; https://doi.org/10.3390/ijms25147961 - 21 Jul 2024
Viewed by 1359
Abstract
Spinal cord injury (SCI) is a severe medical condition resulting in substantial physiological and functional consequences for the individual. People with SCI are characterised by a chronic, low-grade systemic inflammatory state, which contributes to further undesirable secondary injuries. This study aimed to evaluate [...] Read more.
Spinal cord injury (SCI) is a severe medical condition resulting in substantial physiological and functional consequences for the individual. People with SCI are characterised by a chronic, low-grade systemic inflammatory state, which contributes to further undesirable secondary injuries. This study aimed to evaluate the effect of adding aquatic therapy to the standard physiotherapy treatment, implemented in two different schedules, on systemic inflammation in SCI patients. Additionally, the relationship between cytokine blood levels and changes in functionality (measured with the 6MWT, 10MWT, WISCI, BBS, and TUG tests) throughout the study was assessed. A quantitative multiplexed antibody assay was performed to measure the expression level of 20 pro- and anti-inflammatory cytokines in blood samples from SCI patients at three time points: baseline, week 6, and immediately post-intervention (week 12). This study identified a complex signature of five cytokines (IL-12p70, IL-8, MCP-1, IL-1α, and IP10) associated with the time course of the two physiotherapy programs. Two other cytokines (IL-4 and TNF-α) were also associated with the functional recovery of patients. These could be important indicators for SCI prognosis and provide a basis for developing novel targeted therapies. Full article
(This article belongs to the Special Issue Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0)
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11 pages, 2912 KiB  
Article
miR-146a Decreases Inflammation and ROS Production in Aged Dermal Fibroblasts
by Liping Zhang, Iris C. Wang, Songmei Meng and Junwang Xu
Int. J. Mol. Sci. 2024, 25(13), 6821; https://doi.org/10.3390/ijms25136821 - 21 Jun 2024
Cited by 2 | Viewed by 1052
Abstract
Aging is associated with a decline in the functionality of various cell types, including dermal fibroblasts, which play a crucial role in maintaining skin homeostasis and wound healing. Chronic inflammation and increased reactive oxygen species (ROS) production are hallmark features of aging, contributing [...] Read more.
Aging is associated with a decline in the functionality of various cell types, including dermal fibroblasts, which play a crucial role in maintaining skin homeostasis and wound healing. Chronic inflammation and increased reactive oxygen species (ROS) production are hallmark features of aging, contributing to impaired wound healing. MicroRNA-146a (miR-146a) has been implicated as a critical regulator of inflammation and oxidative stress in different cell types, yet its role in aged dermal fibroblasts and its potential relevance to wound healing remains poorly understood. We hypothesize that miR-146a is differentially expressed in aged dermal fibroblasts and that overexpression of miR-146a will decrease aging-induced inflammatory responses and ROS production. Primary dermal fibroblasts were isolated from the skin of 17-week-old (young) and 88-week-old (aged) mice. Overexpression of miR-146a was achieved through miR-146a mimic transfection. ROS were detected using a reliable fluorogenic marker, 2,7-dichlorofluorescin diacetate. Real-time PCR was used to quantify relative gene expression. Our investigation revealed a significant reduction in miR-146a expression in aged dermal fibroblasts compared to their younger counterparts. Moreover, aged dermal fibroblasts exhibited heightened levels of inflammatory responses and increased ROS production. Importantly, the overexpression of miR-146a through miR-146a mimic transfection led to a substantial reduction in inflammatory responses through modulation of the NF-kB pathway in aged dermal fibroblasts. Additionally, the overexpression of miR-146a led to a substantial decrease in ROS production, achieved through the downregulation of NOX4 expression in aged dermal fibroblasts. These findings underscore the pivotal role of miR-146a in mitigating both inflammatory responses and ROS production in aged dermal fibroblasts, highlighting its potential as a therapeutic target for addressing age-related skin wound healing. Full article
(This article belongs to the Special Issue Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0)
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19 pages, 3963 KiB  
Article
The Effect of Orally Administered Multi-Strain Probiotic Formulation (Lactobacillus, Bifidobacterium) on the Phagocytic Activity and Oxidative Metabolism of Peripheral Blood Granulocytes and Monocytes in Lambs
by Roman Wójcik, Joanna Małaczewska, Dawid Tobolski, Jan Miciński, Edyta Kaczorek-Łukowska and Grzegorz Zwierzchowski
Int. J. Mol. Sci. 2024, 25(10), 5068; https://doi.org/10.3390/ijms25105068 - 7 May 2024
Viewed by 1445
Abstract
Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided equally into two groups (C—control and E—experimental). The examined [...] Read more.
Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided equally into two groups (C—control and E—experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (Phagotest) and oxidative metabolism (Phagoburst) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs that were administered the multi-strain probiotic formulation compared with lambs in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate). These findings suggest that the tested probiotic formulation may have a positive effect on the immune status of lambs. Full article
(This article belongs to the Special Issue Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0)
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Review

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37 pages, 1047 KiB  
Review
Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments
by Ahmad Dawalibi, Amal Ahmed Alosaimi and Khalid S. Mohammad
Int. J. Mol. Sci. 2024, 25(15), 8163; https://doi.org/10.3390/ijms25158163 - 26 Jul 2024
Viewed by 1274
Abstract
Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores [...] Read more.
Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in promoting osteoclastogenesis, tumor proliferation, and angiogenesis. These cytokines create a favorable environment for cancer cell survival and bone degradation, contributing to the progression of metastatic lesions. Conversely, anti-inflammatory interleukins, including IL-4, IL-10, and IL-13, exhibit protective roles by modulating immune responses and inhibiting osteoclast activity. Understanding these opposing effects is crucial for developing targeted therapies aimed at disrupting the pathological processes in bone metastases. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, mediate the actions of these interleukins, influencing tumor cell survival, immune cell recruitment, and bone remodeling. Targeting these pathways presents promising therapeutic avenues. Current treatment strategies, such as the use of denosumab, tocilizumab, and emerging agents like bimekizumab and ANV419, highlight the potential of interleukin-targeted therapies in mitigating bone metastases. However, challenges such as therapeutic resistance, side effects, and long-term efficacy remain significant hurdles. This review also addresses the potential of interleukins as diagnostic and prognostic biomarkers, offering insights into patient stratification and personalized treatment approaches. Interleukins have multifaceted roles that depend on the context, including the environment, cell types, and cellular interactions. Despite substantial progress, gaps in research persist, particularly regarding the precise mechanisms by which interleukins influence the bone metastatic niche and their broader clinical implications. While not exhaustive, this overview underscores the critical roles of interleukins in bone metastases and highlights the need for continued research to fully elucidate their complex interactions and therapeutic potential. Addressing these gaps will be essential for advancing our understanding and treatment of bone metastases in cancer patients. Full article
(This article belongs to the Special Issue Pro-inflammatory and Anti-inflammatory Interleukins in Various Diseases 2.0)
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