Interleukin-1.
Interleukin-1 (IL-1) is the prototypic pro-inflammatory cytokine. There are two forms of IL-1, IL-1alpha and IL-1beta and in most studies, their biological activities are indistinguishable. IL-1 affects nearly every cell type, often in concert with another pro-inflammatory cytokine, tumor necrosis factor (TNF). Although IL-1 can upregulate host defenses and function as an immunoadjuvant, IL-1 is a highly inflammatory cytokine. The margin between clinical benefit and unacceptable toxicity in humans is exceedingly narrow. In contrast, agents that reduce the production and/or activity of IL-1 are likely to have an impact on clinical medicine. The synthesis, processing, secretion and activity of IL-1, particularly IL-1beta, are tightly regulated events. A unique aspect of cytokine biology is the naturally occurring IL-1 receptor antagonist (IL-1Ra). IL-1Ra is structurally similar to IL-1beta but lacking agonist activity is used in clinical trials to reduce disease severity. In addition, regulation of IL-1 activity extends to low numbers of surface receptors, circulating soluble receptors and a cell surface "decoy" receptor to down-regulate responses to IL-1beta. This review updates the current knowledge on IL-1.
Dinarello
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CA
Department of Medicine, University of Colorado Health Science Center, Denver 80262, USA.
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000502:physiology; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012795:Sialoglycoproteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D020558:GTP Phosphohydrolases