Interleukin 10 protects mice from lethal endotoxemia

• Published in: The Journal of experimental medicine Vol. 177; no. 4; pp. 1205 - 1208
• Main Authors: HOWARD, M, MUCHAMUEL, T, ANDRADE, S, MENON, S
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01-04-1993; The Rockefeller University Press
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Endotoxins - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Interleukin-1 - biosynthesis; Interleukin-10 - pharmacology; Kinetics; Lymphokines, interleukins ( function, expression); Mice; Mice, Inbred BALB C; Regulatory factors and their cellular receptors; Shock, Septic - immunology; Shock, Septic - prevention & control; Tumor Necrosis Factor-alpha - biosynthesis; Immunomodulation; Interleukin; Rodentia; Cytokine; Endotoxin; Biological activity; Mechanism; Prevention; Vertebrata; Mammalia; Mouse; Interleukin 10; Lipopolysaccharide; Bacteria; Recombinant protein; Endotoxemia
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.177.4.1205

Interleukin 10 (IL-10) decreases production of IL-1, IL-6, and tumor necrosis factor alpha (TNF-alpha) in vitro, and neutralization of IL-10 in mice leads to elevation of the same monokines. We test here whether this monokine-suppressing property of IL-10 confers on it the capacity to protect mice from lipopolysaccharide-induced shock, a monokine-mediated inflammatory reaction. A single injection of 0.5-1 microgram of recombinant murine IL-10 reproducibly protected BALB/c mice from a lethal intraperitoneal injection of endotoxin. This result was obtained whether the IL-10 was administered concurrently with, or 30 min after the injection of endotoxin. The protective effect of IL-10 was reversed by prior injection of neutralizing anti-IL-10 antibodies, and correlated with a substantial decrease in endotoxin-induced TNF-alpha release. These data implicate IL-10 as a candidate for treatment of bacterial sepsis, and more generally as an effective antiinflammatory reagent.