Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis |
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Authors: | Emmanuilidis K Weighardt H Maier S Gerauer K Fleischmann T Zheng X X Hancock W W Holzmann B Heidecke C D |
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Institution: | Department of Surgery, Klinikum rechts der Isar, Technische Universit?t, Ismaninger Strasse 22, 81675 Münich, Germany. |
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Abstract: | 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. |
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