Interleukin-1 receptor antagonist reduces mortality from endotoxin shock

• Published in: Nature (London) Vol. 348; no. 6301; pp. 550 - 552
• Main Authors: Ohlsson, Kjell, Björk, Peter, Bergenfeldt, Magnus, Hageman, Robert, Thompson, Robert C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 06.12.1990; Nature Publishing Group
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Bacteria; Biochemistry; Biological and medical sciences; Blood Pressure - drug effects; Endotoxins - toxicity; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunity (Disease); Immunobiology; Infections; Interleukin-1 - pharmacology; Interleukin-1 - physiology; Lung - pathology; Lymphokines, interleukins ( function, expression); Medical research; Rabbits; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - physiology; Receptors, Interleukin-1; Recombinant Proteins; Regulatory factors and their cellular receptors; Shock, Septic - drug therapy; Shock, Septic - pathology; Time Factors; Shock; Mortality; Cytokine; Rabbit; Histology; Lagomorpha; Endotoxin; Survival; Biological activity; Infection; Vertebrata; Membrane receptor; Mammalia; Interleukin 1; Bacteriosis; Antagonist
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/348550a0

About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy. The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems. Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans. But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin. The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death. We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock.