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

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 suscep...

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Bibliographic Details
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
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.167.7.3919