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Cytokines as Biomarkers for Diagnosis and Treatment of Chronic Inflammatory Conditions: Concerns, Pitfalls, Boundaries and Future Perspectives

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 2537

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Special Issue Editor

Dr. Ljiljana Trtica Majnarić

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Guest Editor

Faculty of Medicine Osijek, Josip Juraj Strossmayer University, Osijek, Croatia
Interests: primary health care; multimorbidity; chronic aging diseases; chronic inflammation

Special Issue Information

Dear Colleagues,

Cytokines are low-weight glycoproteins that mediate communication between immunological cells, but also other activated cells at the inflammation site. The historical classification that is based on first discoveries of action of these substances recognizes several cytokine subgroups, including interleukines (ILs), interferons, cytokines with cytotoxic effects, colony-stimulating factors, chemokines and other cytokines. In a narrow sense, the term “cytokines” involves ILs that primarily originate from immunological cells, cytokines of innate immunity, such as IL-1b, tumor necrosis factor alpha (TNF-a), IL-6, IL-12, IL-18 and IL-23, and cytokines of adaptive immunity, such as IL-2, interferon-gamma (IFN-g), IL-5, IL-9, IL-17 and immunosuppressive cytokines, like IL-4, IL-10, IL-37 and IL-38. Cytokines are biologically very potent compounds, which act in picogrammes, including autocrine (on the cell of origin), paracrine (on nearby cells) and, less often, endocrine (on distant cells) modes of action.

The well-defined cytokine signaling pathways were the basis for the use of a variety of cytokines and molecules as signaling pathways in immunotherapy for a range of inflammatory and autoimmune diseases, including cancers and hematological malignancies. Although immunotherapy has changed the course and outcomes of many diseases with an underlying immune pathogenesis, a decision on when to use such treatment is not always straightforward. This decision is particularly difficult to make in elderly people and in complex chronic conditions associated with the presence of multiple comorbidities. There are no recommendations to use biological therapy in cardio-metabolic conditions, despite evidence indicating a close association between these disorders and chronic inflammation. Particularly challenging is the evaluation of cytokines as diagnostic biomarkers because of their great variability, which depends on changes in physiological conditions, patient lifestyles and on characteristics of the examined population.

The aim of this Special Issue is to provide an update of the efficacy and safety of cytokine-based therapy under real-life conditions, with an emphasis on concerns, pitfalls, boundaries and future perspectives of using this therapy in elderly patients and in complex chronic inflammatory disorders. The aim is also to evaluate the limitations of cytokine diagnostic abilities and define conditions under which cytokines can be used as reliable diagnostic biomarkers. Submissions dealing with the topics mentioned in the keywords listed below are welcome.

Dr. Ljiljana Trtica Majnarić
Guest Editor

Manuscript Submission Information

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Keywords

cytokines
chronic diseases
complex conditions
elderly patient groups
malignancies
therapy
diagnostic abilities
boundaries
perspectives

Published Papers (3 papers)

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Research

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18 pages, 1153 KiB

Open AccessArticle

Decreased IL-1 β Secretion as a Potential Predictor of Tuberculosis Recurrence in Individuals Diagnosed with HIV

by Marina Nosik, Konstantin Ryzhov, Asya V. Kudryavtseva, Ulyana Kuimova, Alexey Kravtchenko, Alexandr Sobkin, Vitaly Zverev and Oxana Svitich

Biomedicines 2024, 12(5), 954; https://doi.org/10.3390/biomedicines12050954 - 25 Apr 2024

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Abstract

Background: The mechanisms of the formation of immunological competence against tuberculosis (TB), and especially those associated with HIV co-infection, remain poorly understood. However, there is an urgent need for risk recurrence predictive biomarkers, as well as for predictors of successful treatment outcomes. The goal of the study was to identify possible immunological markers of TB recurrence in individuals with HIV/TB co-infection. Methods: The plasma levels of IFN-γ, TNF-α, IL-10, and IL-1β (cytokines which play important roles in the immune activation and protection against Mycobacterium tuberculosis) were measured using ELISA EIA-BEST kits. The cytokine concentrations were determined using a standard curve obtained with the standards provided by the manufacturer of each kit. Results: A total of 211 individuals were enrolled in the study as follows: 62 patients with HIV/TB co-infection, 52 with HIV monoinfection, 52 with TB monoinfection, and 45 healthy donors. Out of the 62 patients with HIV/TB, 75.8% (47) of patients were newly diagnosed with HIV and TB, and 24.2% (15) displayed recurrent TB and were newly diagnosed with HIV. Decreased levels of IFN-γ, TNF-α, and IL-10 were observed in patients with HIV/TB when compared with HIV and TB patients. However, there was no difference in IFN-γ, TNF-α, or IL-10 secretion between both HIV/TB groups. At the same time, an almost 4-fold decrease in Il-1β levels was detected in the HIV/TB group with TB recurrence when compared with the HIV/TB group (p = 0.0001); a 2.8-fold decrease when compared with HIV patients (p = 0.001); and a 2.2-fold decrease with newly diagnosed TB patients (p = 0.001). Conclusions: Significantly decreased Il-1β levels in HIV/TB patients’ cohort with secondary TB indicate that this cytokine can be a potential biomarker of TB recurrence. Full article

(This article belongs to the Special Issue Cytokines as Biomarkers for Diagnosis and Treatment of Chronic Inflammatory Conditions: Concerns, Pitfalls, Boundaries and Future Perspectives)

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10 pages, 680 KiB

Open AccessArticle

Interferon Lambda Signaling Restrains Experimental Autoimmune Encephalomyelitis

by Mohammad Asif Sherwani, Samuel J. Duesman, Zdenek Hel, Chander Raman and Nabiha Yusuf

Biomedicines 2024, 12(3), 526; https://doi.org/10.3390/biomedicines12030526 - 26 Feb 2024

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Abstract

IFN-λ is a type III interferon (IFN) with pleiotropic functions in modulating immune responses. To address its function in autoimmune neuroinflammation, we evaluated the development and progression of experimental autoimmune encephalitis (EAE) in IFNLR1 KO (Ifnlr1^−/−) and C57Bl/6 (WT) mice following immunization with MOG₃_5–55 peptide. The results show that Ifnlr1^−/− mice developed significantly more severe EAE than WT littermates with a similar day of onset, suggesting the potential of IFN-λ in reducing disease severity. We next interrogated whether IFN-λ differentially modulates EAE induced by encephalitogenic Th1 cells or Th17 cells. Encephalitogenic Th1 or Th17 generated from WT donors were transferred into WT or Ifnlr1^−/− recipient mice. Whereas encephalitogenic Th1 cells induced more severe EAE in Ifnlr1^−/− than WT recipients, the disease severity induced by encephalitogenic Th17 cells was similar. Additionally, in vitro experiments showed that Ifnlr1^−/− macrophages promoted the expansion of myelin peptide-reactive Th17 cells but not Th1 cells. Early in the disease, the spinal cords of EAE mice displayed a significantly greater proportion of Ly6C^-Ly6G⁺ cells with CXCR2⁺CD62L^lo phenotype, indicating activated neutrophils. These findings suggest that IFN-λ signaling restrains activation and migration of neutrophils to the CNS, potentially attenuating neutrophil-mediated disease progression in autoimmune neuroinflammation. Recombinant IFN-λ can be used as a potential therapeutic target for treatment of patients with multiple sclerosis as it has fewer side effects due to the restricted expression of its receptor. Full article

(This article belongs to the Special Issue Cytokines as Biomarkers for Diagnosis and Treatment of Chronic Inflammatory Conditions: Concerns, Pitfalls, Boundaries and Future Perspectives)

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Review

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24 pages, 1007 KiB

Open AccessReview

Putting Functional Gastrointestinal Disorders within the Spectrum of Inflammatory Disorders Can Improve Classification and Diagnostics of These Disorders

by Dunja Šojat, Mile Volarić, Tanja Keškić, Nikola Volarić, Venija Cerovečki and Ljiljana Trtica Majnarić

Biomedicines 2024, 12(3), 702; https://doi.org/10.3390/biomedicines12030702 - 21 Mar 2024

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Abstract

The spectrum, intensity, and overlap of symptoms between functional gastrointestinal disorders (FGIDs) and other gastrointestinal disorders characterize patients with FGIDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis of FGID and the applicability of a given treatment is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found to cause the continuous existence of a low level of inflammation, which is thought to be a basic pathophysiological process. The idea of the gut–brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and the intestinal functions, including the involvement of gut bacteria. In this review paper, we intend to promote the hypothesis that FGIDs should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic, and microbiome pathways. This hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, that is omnipresent in chronic health conditions. A better understanding of inflammation’s role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs may reduce patient heterogeneity and help clarify the pathophysiology of this disease to allow for better treatment. Full article

(This article belongs to the Special Issue Cytokines as Biomarkers for Diagnosis and Treatment of Chronic Inflammatory Conditions: Concerns, Pitfalls, Boundaries and Future Perspectives)

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