Interleukin-1 receptor antagonist as therapy for inflammatory disorders.
IL-1 is a pivotal mediator of the immune response and has been implicated in inflammatory and infectious diseases. As a consequence, the administration of IL-1 receptor antagonist (IL-1ra), a recombinantly synthesised endogenous inhibitor of IL-1, has appeal as a therapeutic strategy in these conditions. To date, the largest clinical experiences with IL-1ra have been in the setting of sepsis and rheumatoid arthritis (RA). Like other anti-inflammatory agents that target a specific mediator, IL-1ra was found to lack efficacy when given in conjunction with standard therapy in patients with sepsis and septic shock. In contrast, recent studies enrolling patients with RA suggest that IL-1ra significantly ameliorates disease activity and retards joint destruction. Whether the respective lack of efficacy and success of IL-1ra in these two diseases is a result of differences in the pathologic processes involved, or reflects the nature in which the clinical studies were conducted, is unclear. Further, the effectiveness of IL-1ra compared to other anticytokine and conventional treatments in RA remains to be clarified. Nonetheless, the recent finding that IL-1ra has the ability to favourably influence a chronic inflammatory disease supports the hypothesis that inhibition of a single mediator of the immune response may have clinical impact.
Freeman
B D
BD
Department of Surgery, Section of Burn, Trauma & Surgical Critical Care, Washington University School of Medicine, St. Louis, MO, USA. freemanb@msnotes.wustl.edu
Buchman
T G
TG
D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D012795:Sialoglycoproteins / Q000276:immunology / Q000627:therapeutic use*; D016896:Treatment Outcome
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins