Critical Role of Kupffer Cell-Derived IL-10 for Host Defense in Septic Peritonitis

• Published in: The Journal of immunology (1950) 2001-10, Vol.167 (7), p.3919-3927
• Main Authors: Emmanuilidis, Klaus, Weighardt, Heike, Maier, Stefan, Gerauer, Klaus, Fleischmann, Tanja, Zheng, Xin X, Hancock, Wayne W, Holzmann, Bernhard, Heidecke, Claus-Dieter
• Format: Article
• Language: English
• Subjects: Animals; Bacteremia - drug therapy; Bacteremia - immunology; Clodronic Acid - pharmacology; Cytokines - blood; Female; g-Interferon; Interferon-gamma - biosynthesis; Interleukin-10 - genetics; Interleukin-10 - pharmacology; Interleukin-10 - physiology; Kinetics; Kupffer Cells - immunology; Liver - immunology; Lung - immunology; Mice; Mice, Inbred C57BL; Peritonitis - drug therapy; Peritonitis - immunology; RNA, Messenger - biosynthesis; Spleen - immunology; Survival Rate
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.7.3919

Intra-abdominal infection in patients following major visceral surgery is associated with high mortality. Using a macrophage depletion technique, we demonstrate that in murine septic peritonitis, Kupffer cells are a major source of systemic IL-10 levels. Kupffer cell-depleted mice were highly susceptible to the lethal effects of septic peritonitis and exhibited an increased bacterial load. Kupffer cell-depleted mice were protected by the administration of an IL-10-Fc fusion protein. Loss of Kupffer cell-derived IL-10 was associated with a weak increase in serum IL-12 levels, whereas TNF, IL-1alpha, and IL-18 levels were not significantly elevated, suggesting that the loss of Kupffer cell-derived IL-10 did not result in a toxic cytokine release syndrome. Instead, loss of Kupffer cell-derived IL-10 was associated with a reduced splenocyte production of IFN-gamma that is required for immune protection in murine septic peritonitis. Therefore, the results suggest that the protective function of IL-10 in septic peritonitis may not be restricted to the anti-inflammatory activities of IL-10.