title: Role of IL-10 in regulating proinflammatory cytokine release by Kupffer cells following trauma-hemorrhage.
abstract: IL-6 and TNF-alpha production by Kupffer cells is markedly stimulated following trauma-hemorrhage (T-H). Because IL-10 is an anti-inflammatory cytokine, the aim of this study was to determine whether IL-10 regulates Kupffer cell proinflammatory cytokine release following T-H. To study this, we subjected adult male Sprague-Dawley rats to sham operation or T-H. The procedure involved a 5-cm midline laparotomy and approximately 90 min of hemorrhagic shock (35 mmHg), followed by resuscitation with four times the shed blood volume in the form of Ringer's lactate. At 2 h after the end of resuscitation, livers were perfused in vitro and perfusate was collected. In separate studies, Kupffer cells were isolated and incubated with different concentrations of anti-IL-10 MAb. IgG was used as control. After 16 h of incubation, IL-6 and TNF-alpha levels were measured by ELISA. Plasma IL-10 levels increased significantly following T-H. IL-10 levels in the perfusate and IL-10 production by cultured Kupffer cells were also significantly higher in the T-H group. When Kupffer cells were incubated with 10 microg/ml of anti-IL-10 MAb, IL-6 and TNF-alpha production were significantly increased in both sham and T-H groups compared with those not treated with anti-IL-10 MAb. However, these changes were not observed when the cells were incubated with irrelevant (control) IgG. These results indicate that IL-10 production by Kupffer cells early after T-H may play a pivotal role in attenuating the proinflammatory cytokine environment, possibly in an autocrine/paracrine manner.
authors.affiliation: Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, 35294-0019, USA.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: William C
authors.initials: WC
authors.lastname: Kitchens
authors.forename: Balazs
authors.initials: B
authors.lastname: Toth
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Loring W
authors.initials: LW
authors.lastname: Rue
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D006470:Hemorrhage / Q000209:etiology* / Q000378:metabolism*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014950:Wounds, Penetrating / Q000150:complications*
chemical_list: D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10