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IL-6 in Inflammation, Immunity, and Disease

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TLDR
The mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
Abstract
Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions. Although its expression is strictly controlled by transcriptional and posttranscriptional mechanisms, dysregulated continual synthesis of IL-6 plays a pathological effect on chronic inflammation and autoimmunity. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody was developed. Various clinical trials have since shown the exceptional efficacy of tocilizumab, which resulted in its approval for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Moreover, tocilizumab is expected to be effective for other intractable immune-mediated diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.

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SARS-CoV-2 infection: The role of cytokines in COVID-19 disease.

TL;DR: This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit to support the design of more effective approaches to the management of CO VID-19.
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Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies.

TL;DR: It is shown that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes, and the current evidence indicates that tocilizumab, an IL- 6 inhibitor, is relatively effective and safe.
Journal ArticleDOI

Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated With Drastically Elevated Interleukin 6 Level in Critically Ill Patients With Coronavirus Disease 2019.

TL;DR: Detectable serum SARS-Cov-2 RNA(RNAaemia) in COVID-19 patients was associated with elevated IL-6 concentration and poor prognosis, andIL-6 could be a potential therapeutic target for critically ill patients with an excessive inflammatory response.
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Immunotherapeutic implications of IL-6 blockade for cytokine storm

TL;DR: The possibility that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis is proposed.
Journal ArticleDOI

Targeting Interleukin-6 Signaling in Clinic

TL;DR: The current state of IL-6-targeting approaches in the clinic is reviewed and how to apply the growing understanding of the immunobiology ofIL-6 to clinical decisions is discussed.
References
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Journal ArticleDOI

Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.

TL;DR: It is shown that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β, and the data demonstrate a dichotomy in thegeneration of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T Cells that inhibit autoimmune tissue injury.
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The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.

TL;DR: It is shown that the orphan nuclear receptor RORgammat is the key transcription factor that orchestrates the differentiation of this effector cell lineage of proinflammatory T helper cells and its potential as a therapeutic target in inflammatory diseases is highlighted.
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Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages

TL;DR: Findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
Journal ArticleDOI

IL-17 and Th17 Cells.

TL;DR: The investigation of the differentiation, effector function, and regulation of Th17 cells has opened up a new framework for understanding T cell differentiation and now appreciate the importance of Th 17 cells in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.
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