Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases

Akdiş, Mübeccel; Aab, Alar; Altunbulakli, Can; Azkur, Kursat A; Costa, Rita; Crameri, Reto; Duan, Su; Eiwegger, Thomas; Eljaszewicz, Andrzej; Ferstl, Ruth; Frei, Remo; Garbani, Mattia; Głobińska, Anna; Hess, Lena; Huitema, Carly; Kubo, Terufumi; Komlósi, Zsolt István; Konieczna, Patrycja; Kovács, Nóra; Küçüksezer, Umut Can; Meyer, Norbert; Morita, Hideaki; Olzhausen, Judith; O’Mahony, Liam; Pezer, Marija; Prati, Moira; Rebane, Ana; Rhyner, Claudio; Rinaldi, Arturo; Sokołowska, Milena; Stanić, Barbara; Sugita, Kazunari; Treis, Angela; Veen, Willem van de; Wanke, Kerstin; Wawrzyniak, Marcin; Wawrzyniak, Paulina; Wirz, Oliver F.; Zakzuk, Josefina

doi:10.1016/j.jaci.2016.06.033

Cited by 702 publications

(702 citation statements)

References 217 publications

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“…Li et al reported an extracellular function of the IL-37 precusor, which suppresses LPS-induced IL-6 production in human M1 differentiated macrophages (49). IL-37 acts as an extracellular cytokine by binding to the IL-18 receptor and requires the IL-1 family decoy receptor IL-1R8 for its anti-inflammatory function (49) It has been shown that these pro-inflammatory cytokines (TNF-α, IL-1α, IL-1β, IFN-γ) could play pivotal roles in experimental autoimmune thyroiditis, multiple sclerosis, insulin-dependent diabetes mellitus or experimental autoimmune diabetogenesis, which may indirect suggest the biological and potentially therapeutic relevance of IL-37 to these diseases (50)(51)(52)(53)(54)(55). However, it remains unknown whether nuclear translocation of IL-37 is the only mechanism that leads to reduction in cytokine expressions.…”

Section: The Function Of Il-37mentioning

confidence: 99%

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

et al. 2018

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Abstract. Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions. In addition, IL-37 may prove to be a new and potentially useful target for effective cytokine therapy. Further evidence is needed to clarify in more detail the effects of IL-37 in experimental and clinical studies. Based on an extensive summary of published data, the aim of this review is to outline the current knowledge of IL-37, including the location, structure, expression, regulation and function, as well as the potential clinical applications of this cytokine.

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Section: The Function Of Il-37mentioning

confidence: 99%

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

et al. 2018

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“…There are 38 interleukins which are designated by the abbreviation IL (from Interleukin) and Arabic numbers [19]. Interleukins are produced by various types of body cells, wherein the speciic interleukins (IL-1) can be secreted by up to 20 diferent cell types.…”

Section: Interleukinsmentioning

confidence: 99%

Physiology and Pathology of Cytokine: Commercial Production and Medical Use

Zdravković¹,

Rosić²,

Lutovac³

et al. 2017

Physiology and Pathology of Immunology

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Cytokines are small, short-lived proteins secreted by many diferent cell types. As signaling molecules, cytokines provide communication between cells and play a crucial role in modulating innate and adaptive immune response. The family of cytokines includes interferons, interleukins, chemokines, mesenchymal growth factors, tumor necrosis factor family and adipokines. Interferons (IFNs) are a multigene family of inducible cytokines with antiviral, antiproliferative, and immunomodulatory function. Recombinant DNA technology can be useful in the production of human IFNs. This process includes fermentation, puriication, and formation of the inal product. Interleukins are classiied in families based on sequence homology, receptor-binding properties, biological function, and cellular sources. TNF and IL-1 are considered to be key mediators of inlammatory response, while IL-6 plays a key role in the transition from acute to chronic inlammation. The inhibition of TNF includes administration of anti-TNF antibody and TNF receptor (TNFR). The reduction of IL-1 level can be achieved by the administration of anti-IL-1 antibody or IL-1 receptor antagonist (IL-1Ra), and the reduction of IL-6 level in the treatment of chronic inlammatory diseases can be achieved by the administration of anti-IL-6 antibody and anti-IL-6 receptor antibody. Recombinant cytokines and cytokine antagonists (antibodies and receptors) can be used in treating many diferent diseases.

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“…The TGF-β family consists of TGF-β1, TGF-β2, and TGF-β3 which are produced by a variety of cells including fibroblasts, platelets, mast cells, monocytes, macrophages, and Tregs [135].…”

Section: Tgf-βmentioning

confidence: 99%

Systemic and local regulation of experimental arthritis by IFN-α, dendritic cells and uridine

Narendra¹

2017

Linköping University Medical Dissertations

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In this thesis, we have studied the immunological processes of joint inflammation that may be targets for future treatment of patients with arthritis. We focus on the immune-modulating properties of interferon-α (IFN-α) and uridine in experimental arthritis. The nucleoside uridine, which is regarded a safe treatment has anti-inflammatory properties notably by inhibiting tumor necrosis factor (TNF) release. Because the inflamed synovium in rheumatoid arthritis (RA) is characterised by pathogenic TNF-production, uridine could potentially be away to ameliorate arthritis. Systemic administration of uridine had no effect on antigeninduced arthritis (AIA), which is a T-cell dependent model where animals are immunized twice (sensitization) with bovine serum albumin (mBSA), before local triggering of arthritis by intra-articular antigen (mBSA) re-challenge. In contrast, intra-articular administration of uridine clearly down modulated development of AIA in a dose dependent manner and inhibited the expression of synovial adhesion molecules, influx of inflammatory leukocytes and synovial expression of TNF and interleukin 6, but did not affect systemic levels of proinflammatory cytokines or antigen-specific T-cell responses. Local administration of uridine may thus be a viable therapeutic option for treatment of arthritis in the future. Viral double-stranded deoxyribonucleic acid (dsRNA), a common nucleic acid found in most viruses, can be found in the joints of RA patients and local deposition of such viral dsRNA induces arthritis by activating IFN-α. Here we show that arthritis induced by dsRNA can be mediated by IFN-producing dendritic cells in the joint and this may thus explain why viral infections are sometimes associated with arthritis. Earlier, to study the effect of dsRNA and IFN-α in an arthritis model, that like RA, is dependent on adaptive immunity, dsRNA and IFN-α were administered individually during the development of AIA. Both molecules clearly protected against AIA in a type I IFN receptor-dependent manner but were only effective if administered in the sensitization phase of AIA. Here we show that the anti-inflammatory effect of IFN-α is critically dependent on signalling via transforming growth factor β (TGF-β) and the enzymatic activity of indoleamine 2,3 dioxygenase 1 (IDO). The IDO enzyme is produced by plasmacytoid DC and this cell type was critically required both during antigen sensitization and in the arthritis phase of AIA for the protective effect of IFN-α against AIA. In contrast, TGF-β and the enzymatic activity of IDO were only required during sensitization, which indicate that they are involved in initial steps of tolerogenic antigen sensitization. In this scenario, IFN- α first activates the enzymatic activity of IDO in pDC, which converts Tryptophan to Kynurenine, which thereafter activates TGF-β. Common for IDO-expressing pDC, Kyn and TGF-β is their ability to induce development of regulatory T cells (Tregs). We found that Tregs were crucial for IFN-α-mediated protection against AIA, but onl...

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Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases

Cited by 702 publications

References 217 publications

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

Physiology and Pathology of Cytokine: Commercial Production and Medical Use

Systemic and local regulation of experimental arthritis by IFN-α, dendritic cells and uridine

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