title: Neutrophil IL-10 suppresses peritoneal inflammatory monocytes during polymicrobial sepsis.
abstract: Septic peritonitis remains a major cause of death. Neutrophils and inflammatory monocytes are principal components of the innate immune system and are essential for defense against a range of microbial pathogens. Their role and interaction in polymicrobial sepsis have not been defined clearly. Using a murine model of CLP to induce moderate sepsis, we found that neutrophil depletion did not alter survival, whereas depletion of neutrophils and inflammatory monocytes markedly reduced survival. After neutrophil depletion, inflammatory monocytes had greater phagocytic capacity and oxidative burst, and increased expression of costimulatory molecules, TNF, and iNOS. Notably, peritoneal neutrophils produced IL-10 following CLP. Adoptive i.p. transfer of WT but not IL-10(-/-) neutrophils into septic mice reduced monocyte expression of TNF. In vitro experiments confirmed that monocyte suppression was mediated by neutrophil-derived IL-10. Thus, during septic peritonitis, neutrophils suppress peritoneal inflammatory monocytes through IL-10 and are dispensable for survival.
authors.affiliation: Hepatopancreatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Ocuin
authors.forename: Zubin M
authors.initials: ZM
authors.lastname: Bamboat
authors.forename: Vinod P
authors.initials: VP
authors.lastname: Balachandran
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cavnar
authors.forename: Hebroon
authors.initials: H
authors.lastname: Obaid
authors.forename: George
authors.initials: G
authors.lastname: Plitas
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
mesh_terms: D000818:Animals; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000201:enzymology / Q000473:pathology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010538:Peritonitis / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D018805:Sepsis / Q000150:complications / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II