Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia

• Published in: The Journal of experimental medicine 1993-02, Vol.177 (2), p.547-550
• Main Authors: GERARD, C, BRUYNS, C, MARCHANT, A, ABRAMOWICZ, D, VANDENABEELE, P, DELVAUX, A, FIERS, W, GOLDMAN, M, VELU, T
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Endotoxins - toxicity; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hypothermia - prevention & control; Immunobiology; Interleukin-10 - pharmacology; Lipopolysaccharides - toxicity; Mice; Mice, Inbred BALB C; Modulation of the immune response (stimulation, suppression); Molecular Sequence Data; Oligodeoxyribonucleotides - chemistry; Secretory Rate - drug effects; Shock, Septic - prevention & control; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.177.2.547

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.