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Journal ArticleDOI

Immunological and Inflammatory Functions of the Interleukin-1 Family

Charles A. Dinarello
- 20 Mar 2009 - 
- Vol. 27, Iss: 1, pp 519-550
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TLDR
The IL-1 family includes members that suppress inflammation, both specifically within the IL-2 family but also nonspecifically for TLR ligands and the innate immune response.
Abstract
More than any other cytokine family, the interleukin (IL)-1 family is closely linked to the innate immune response. This linkage became evident upon the discovery that the cytoplasmic domain of the IL-1 receptor type I is highly homologous to the cytoplasmic domains of all Toll-like receptors (TLRs). Thus, fundamental inflammatory responses such as the induction of cyclooxygenase type 2, increased expression of adhesion molecules, or synthesis of nitric oxide are indistinguishable responses of both IL-1 and TLR ligands. Both families nonspecifically affect antigen recognition and lymphocyte function. IL-1β is the most studied member of the IL-1 family because of its role in mediating autoinflammatory diseases. Although the TLR and IL-1 families evolved to assist in host defense against infection, unlike the TLR family, the IL-1 family also includes members that suppress inflammation, both specifically within the IL-1 family but also nonspecifically for TLR ligands and the innate immune response.

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Citations
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Journal ArticleDOI

Activation and regulation of the inflammasomes

TL;DR: The complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response are discussed, and the similarities to another molecular signalling platform — the apoptosome — that monitors cellular health are highlighted.
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Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression.

TL;DR: It is shown that cell priming through multiple signaling receptors induces NLRP3 expression, which is identified to be a critical checkpoint for NLRP2 activation and signals provided by NF-κB activators are necessary but not sufficient forNLRP3 activation.
Journal ArticleDOI

Inflammasomes: mechanism of assembly, regulation and signalling

TL;DR: This Review discusses the recent developments in inflammasome research with a focus on the molecular mechanisms that govern inflammaome assembly, signalling and regulation.
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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance

TL;DR: It is established that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity, and that the NlrP3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
References
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Journal ArticleDOI

Biologic basis for interleukin-1 in disease

TL;DR: This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references, which summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
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IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines

TL;DR: A member of theIL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T( H)2 cells is reported.
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Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.

TL;DR: The results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages, likely that resolution of inflammation depends not only on the removal of apoptosis but on active suppression of inflammatory mediator production.
Journal ArticleDOI

Cloning of a new cytokine that induces IFN-gamma production by T cells.

TL;DR: The cloning of a recently identified IFN-γ-inducing factor (IGIF) that augments natural killer activity in spleen cells and may be involved in the development of Thl cells and also in mechanisms of tissue injury in inflammatory reactions is reported.
Journal ArticleDOI

Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells.

TL;DR: These results identify cytokines, antigen-presenting cells and microbial products that promote the polarization of human TH-17 cells and emphasize an important difference in the requirements for the differentiation of TH- 17 cells in humans and mice.
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