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 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.
Emmanuilidis
K
K
Department of Surgery, Klinikum rechts der Isar, Technische Universität, Ismaninger Strasse 22, 81675 Münich, Germany.
Weighardt
H
H
Maier
S
S
Gerauer
K
K
Fleischmann
T
T
Zheng
X X
XX
Hancock
W W
WW
Holzmann
B
B
Heidecke
C D
CD
D000818:Animals; D016470:Bacteremia / Q000188:drug therapy / Q000276:immunology*; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D007728:Kupffer Cells / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D015996:Survival Rate
D016207:Cytokines; D012333:RNA, Messenger; D004002:Clodronic Acid; D016753:Interleukin-10; D007371:Interferon-gamma