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Attenuation of Inflammatory Disease by Reduction of Interleukin-1 Production or Receptor Antagonism

  • C. A. Dinarello
Conference paper
Part of the Colloquium der Gesellschaft für Biologische Chemie 11.–13. April 1991 in Mosbach/Baden book series (MOSBACH, volume 42)

Abstract

Interleukin-1 (IL-1) is a 17-kDa pro-inflammatory cytokine synthesized from a variety of cell types primarily in association with disease states or during host perturbation such as immune responses. At pM or even fM concentrations, IL-1 triggers various responses in nearly all cells. It appears that there is little or no major role for IL-1 in homeostatic mechanisms. There are two IL-l’s (α and β) each with its distinct sequence; there are two IL-1 receptors. Disease states such as local and systemic infection, septic shock, degenerative arthritis, and autoimmune diseases such as nephritis, vasculitis, and inflammatory bowel disease appear to be mediated, in part, by IL-1. Organ failure, capillary leak, and death occur in animals after a combination of tumor necrosis factor (TNF) and EL-1 which is more effective in inducing these changes than either cytokine alone. IL-1 is also a potent inducer of the endothelial cell adhesion molecules, IL-6, and IL-8, a neutrophil chemotactic and activating factor. Strategies for reducing the effects of IL-1 have been based on suppression of transcription, translation, or secretion; more recently, receptor blockade has been a new approach. A naturally occurring IL-l-specific receptor antagonist (IL-lra), which shares 40% conserved amino acid homology with IL-lb, binds to IL-1 surface receptors with the same affinity as IL-1 but does not possess agonist activity and acts as a competitive inhibitor of IL-1. Studies using the IL-lra to block endogenous IL-1 in a variety of animal disease models suggest that IL-1 plays a key role in triggering the cascade of inflammatory responses. In addition, the IL-lra reduces the spontaneous production of growth factors and proliferation of leukemic cells. The IL-lra may be an advantageous therapy in patients with sepsis, diabetes, inflammatory bowel disease, arthritis, and cancer.

Keywords

Cytokine Synthesis Lipoxygenase Product Myelogenous Leukemia Cell Tumor Necrosis Factor Synthesis Separate Gene Product 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • C. A. Dinarello
    • 1
  1. 1.Department of MedicineTufts University School of Medicine and New England Medical CenterBostonUSA

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