Interleukin-1 and its receptor.
Interleukin-1 (IL-1) is a polypeptide that is produced during infection, injury, or immunologic challenge. There are two molecular forms, IL-1-beta and IL-1-alpha, and despite only a 26% amino acid homology, both forms induce a wide variety of biological changes. These include systemic effects such as fever, sleep, ACTH release, and increased sodium excretion. In vitro, IL-1 activates T and B lymphocytes and induces a variety of lymphokines, interferons, and other cytokines, particularly tumor necrosis factor, for the induction of inflammatory changes such as prostaglandin synthesis, activation of endothelial cells, and bone resorption. Despite the broad range of tissue targets, IL-1 receptors have been described primarily on lymphocyte lines and fibroblasts. A feature of these studies is the low numbers of receptor sites and a relatively low-affinity binding. There is also evidence for the existence of a second class of high-affinity receptors. Molecular weights of IL-1 receptors vary with the cell source; these have been demonstrated with molecular weight of 80, 70, and 60 kDa. In general, there is a discrepancy between receptor number and affinity and biological responses to IL-1. One explanation for the mechanism of action of IL-1, particularly on T cells, is the requirement for cross-linking of two membrane proteins. In some cells, the binding of IL-1 to putative receptors may be fast and transient, accounting for activation of intracellular responses without a measureable biological response (such as increased DNA synthesis). IL-1 activation of cells is an important biological response, and its mechanism remains in an unexplored domain.
Dinarello
C A
CA
Department of Medicine and Pediatrics, Tufts University School of Medicine, Boston, Massachusetts.
Savage
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N
D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D051381:Rats; D011971:Receptors, Immunologic / Q000145:classification / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017472:Receptors, Interleukin-1; D015398:Signal Transduction
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1