title: Endogenous IL-10 protects mice from death during septic peritonitis.
abstract: IL-10 production during endotoxic shock is part of a protective mechanism that involves IL-10-induced inhibition of TNF synthesis. We sought to determine the role of IL-10 in septic peritonitis induced by cecal ligation and puncture (CLP). CLP led to a rapid induction of IL-10 mRNA in various organs of C57BI/6 mice. In liver, IL-10 mRNA was detectable within 1 h following CLP, while in spleen and lungs, IL-10 mRNA was detected from 2 to 4 h and onward. IL-10 protein became detectable in plasma 2 h after CLP, reaching peak concentrations after 12 h (12.7 +/- 5.7 ng/ml). Pretreatment (-2 h) with anti-IL-10 mAb resulted in higher plasma TNF levels following CLP when compared with mice treated with control mAb. Plasma IL-1 activity and IFN-gamma remained undetectable in virtually all mice. Anti-IL-10 enhanced mortality after CLP (p < 0.05 by log-rank test). Addition of anti-TNF mAb did not influence the increased mortality associated with anti-IL-10 treatment. Septic peritonitis is associated with sustained production of IL-10 in various organs, which serves to protect the host against lethality.
authors.affiliation: Cornell University Medical College, Department of Surgery, New York, NY 10021, USA.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: A
authors.initials: A
authors.lastname: Marchant
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
authors.forename: L
authors.initials: L
authors.lastname: Berman
authors.forename: C V
authors.initials: CV
authors.lastname: Keogh
authors.forename: D D
authors.initials: DD
authors.lastname: Lazarus
authors.forename: L
authors.initials: L
authors.lastname: Nguyen
authors.forename: M
authors.initials: M
authors.lastname: Goldman
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000818:Animals; D001483:Base Sequence; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood; D017931:DNA Primers; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010538:Peritonitis / Q000150:complications / Q000276:immunology* / Q000401:mortality; D012333:RNA, Messenger / Q000032:analysis; D018805:Sepsis / Q000209:etiology / Q000276:immunology* / Q000401:mortality
chemical_list: D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D016753:Interleukin-10