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The IL-1 family: The role of IL-1 and IL-18 in inflammation

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Cytokines and Joint Injury

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

IL-1 and its related family member IL-18 are primarily proinflammatory cytokines by their ability to stimulate the expression of genes associated with inflammation and autoimmune diseases. The most salient and relevant properties of IL-1 in inflammation are the initiation of cyclooxygenase type 2 (COX-2), type 2 phospholipase A and inducible nitric oxide syntha se (iNOS). This accounts for the large amount of prostaglandin-E2 (PGE2), platelet activating factor, leukotrienes and nitric oxide (NO) produced by cells exposed to IL-1 or in animals or humans injected with IL-1. Another important proinflammatory property of IL-1 is its ability to increase the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) on mesenchymal cells and vascular-cell adhesion molecule-1 (VCAM-1) on endothelial cells. This latter property promotes the infiltration of inflammatory and immunocompetent cells into the extravascular space. IL-1 is also an angiogenic factor and plays a role in tumor metastasis and blood vessel supply [1]. Mice lacking IL-1 receptors fail to develop proliferative lesions of vascular smooth muscle cells in mechanically injured arteries. In humans with rheumatoid arthritis (RA), the inflammation and joint destructive nature of the disease is reduced with systemic injections of the IL-1 receptor antagonist (IL-1Ra), a member of the IL-1 family that prevents IL-1 activity. However, in addition to these and other proinflammatory properties, IL-1 is also an adjuvant during antibody production and acts on bone marrow stem cells for differentiation in the myeloid series. In fact, unlike TNF, IL-1 is a bone marrow stimulant and was used to treat patients with bone marrow suppression in order to reduce the nadir of thrombocytopenia [2].

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  1. Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, 4200 East Ninth Ave., B168, Denver, CO, 80262, USA

    Charles A. Dinarello

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  1. Rheumatology Research Lab, University Medical Center Nijmegen, 189, Geert Grooteplein 26–28, Nijmegen, 6500 HB, The Netherlands

    Wim B. van den Berg

  2. Hôpital Edouard Herriot Service de Rhumatologie Unité d’Immunologie Clinique, Université Claude Bernard — Lyon 1, Lyon, 69437, France

    Pierre Miossec

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Dinarello, C.A. (2004). The IL-1 family: The role of IL-1 and IL-18 in inflammation. In: van den Berg, W.B., Miossec, P. (eds) Cytokines and Joint Injury. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7883-8_2

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  • DOI: https://doi.org/10.1007/978-3-0348-7883-8_2

  • Publisher Name: Birkhäuser, Basel

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