Interleukin-1 and interleukin-1 receptor antagonist.
Cytokines are produced in disease or during immunologic challenge. Some cytokines increase host resistance to disease whereas others trigger inflammatory processes. Interleukin 1 (IL-1) and tumor necrosis factor (TNF) are pro-inflammatory cytokines that affect nearly every cell either alone or in a synergistic fashion. In animal models of infectious, inflammatory or metastatic disease, the role of IL-1 and TNF has been defined by specifically blocking these cytokines. For TNF, anti-TNF monoclonal antibodies and soluble receptors reduce inflammation and lethality. Antibodies to type I IL receptor, IL-1 receptor antagonist (IL-1ra), and soluble IL-1 receptor have been used to reduce the severity of disease in various animal models of local and systemic inflammation. In a Phase III trial, IL-1ra reduced mortality rate in patients with septic shock syndrome by 22%. IL-1ra and soluble receptors to TNF are produced naturally and are elevated in the circulation in several diseases. It is unclear whether these endogenous levels are sufficient to block IL-1 and TNF from triggering their respective cell-bound receptors in disease. IL-1 infusions into patients induce circulating levels of IL-1ra but not IL-1. TNF infusions into patients also induce high levels of soluble TNF receptors.
Dinarello
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CA
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
D000818:Animals; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D012795:Sialoglycoproteins / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins