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      Overview of the IL‐1 family in innate inflammation and acquired immunity

      1 , 2
      Immunological Reviews
      Wiley

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          Summary

          The interleukin‐1 (IL‐1) family of cytokines and receptors is unique in immunology because the IL‐1 family and Toll‐like receptor (TLR) families share similar functions. More than any other cytokine family, the IL‐1 family is primarily associated with innate immunity. More than 95% of living organisms use innate immune mechanisms for survival whereas less than 5% depend on T‐ and B‐cell functions. Innate immunity is manifested by inflammation, which can function as a mechanism of host defense but when uncontrolled is detrimental to survival. Each member of the IL‐1 receptor and TLR family contains the cytoplasmic Toll‐IL‐1‐Receptor (TIR) domain. The 50 amino acid TIR domains are highly homologous with the Toll protein in Drosophila. The TIR domain is nearly the same and present in each TLR and each IL‐1 receptor family. Whereas IL‐1 family cytokine members trigger innate inflammation via IL‐1 family of receptors, TLRs trigger inflammation via bacteria, microbial products, viruses, nucleic acids, and damage‐associated molecular patterns (DAMPs). In fact, IL‐1 family member IL‐1a and IL‐33 also function as DAMPs. Although the inflammatory properties of the IL‐1 family dominate in innate immunity, IL‐1 family member can play a role in acquired immunity. This overview is a condensed update of the IL‐1 family of cytokines and receptors.

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          Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

          Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.
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            Pyroptosis: host cell death and inflammation.

            Eukaryotic cells can initiate several distinct programmes of self-destruction, and the nature of the cell death process (non-inflammatory or proinflammatory) instructs responses of neighbouring cells, which in turn dictates important systemic physiological outcomes. Pyroptosis, or caspase 1-dependent cell death, is inherently inflammatory, is triggered by various pathological stimuli, such as stroke, heart attack or cancer, and is crucial for controlling microbial infections. Pathogens have evolved mechanisms to inhibit pyroptosis, enhancing their ability to persist and cause disease. Ultimately, there is a competition between host and pathogen to regulate pyroptosis, and the outcome dictates life or death of the host.
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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.

              Cytokines of the interleukin-1 (IL-1) family, such as IL-1 alpha/beta and IL-18, have important functions in host defense, immune regulation, and inflammation. Insight into their biological functions has led to novel therapeutic approaches to treat human inflammatory diseases. Within the IL-1 family, IL-1 alpha/beta, IL-1Ra, and IL-18 have been matched to their respective receptor complexes and have been shown to have distinct biological functions. The most prominent orphan IL-1 receptor is ST 2. This receptor has been described as a negative regulator of Toll-like receptor-IL-1 receptor signaling, but it also functions as an important effector molecule of T helper type 2 responses. We report a member of the IL-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. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.

                Author and article information

                Journal
                Immunological Reviews
                Immunological Reviews
                Wiley
                0105-2896
                1600-065X
                January 2018
                December 16 2017
                January 2018
                : 281
                : 1
                : 8-27
                Affiliations
                [1 ] Department of Medicine University of Colorado Denver Aurora CO USA
                [2 ] Department of Medicine Radboud University Medical Center Nijmegen The Netherlands
                Article
                10.1111/imr.12621
                5756628
                29247995
                22e198af-94c7-48dc-8fc3-62c9306d5597
                © 2018

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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