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A specific receptor antagonist for interleukin 1 prevents Escherichia coli ‐induced shock in rabbits
Author(s) -
Wakabayashi Go,
Gelfand Jeffrey A.,
Burke John F.,
Thompson Robert C.,
Dinarello Charles A.
Publication year - 1991
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.5.3.1825816
Subject(s) - receptor antagonist , septic shock , agonist , interleukin 1 receptor antagonist , receptor , sepsis , tumor necrosis factor alpha , shock (circulatory) , interleukin , cytokine , antagonist , escherichia coli , immunology , endocrinology , pharmacology , biology , medicine , biochemistry , gene
Despite antibiotic therapy, the septic shock syndrome continues to have a high mortality. Tumor necrosis factor (TNF) and interleukin 1 (IL 1), two polypeptide cytokines produced during sepsis, are thought to mediate the hypotension and tissue damage of shock. In the present studies, rabbits were infused with Escherichia coli organisms to produce shock. The IL 1 receptor antagonist (IL 1ra), which competes with IL 1 for occupancy of the IL 1 cell‐surface receptors without agonist properties, was given 15 min before the bacterial infusion and during the subsequent 4 h. In saline‐treated controls, hypotension was sustained for 4 h and death occurred for two of five rabbits; in rabbits treated with the IL 1ra, however, blood pressure was only transiently decreased, returned to pre‐ E. coli levels, and no deaths occurred. The associated leukopenia was also reduced by treatment with the antagonist ( P < 0.05). Histological examination of lung tissues showed reduced infiltrating neutrophils in the IL 1ra treatment group. Despite the attenuated responses in animals treated with the IL 1ra, circulating TNF and IL 1 levels were nearly identical in both groups. We conclude that specific blockade of IL 1 at the receptor level demonstrates an essential role for this cytokine in the pathogenesis of septic shock.—Wakabayashi, G.; Gelfand, J. A.; Burke, J. F.; Thompson, R. C.; Dinarello, C. A. A specific receptor antagonist for interleukin 1 prevents Escherichia coli ‐induced shock in rabbits. FASEB J. 5: 338–343; 1991.