title: The role of interleukin-10 in the regulation of the systemic inflammatory response following trauma-hemorrhage.
abstract: Pro-inflammatory cytokine release after shock is central in the development of subsequent multiple organ dysfunction syndrome. Some studies suggest that interleukin-10 (IL-10) is an immunosuppressive mediator after injury or sepsis, while others suggest that IL-10 is an important regulator of the pro-inflammatory response. We hypothesized that in a model of trauma and hemorrhagic shock (TH), IL-10 regulates pro-inflammatory cytokine activity via an autocrine effect on cytokine mRNA transcription in Kupffer cells early after TH. To study this, male C3H/HeN mice were sham-operated or subjected to TH. Plasma levels of TNF-alpha, IL-6 and PGE(2) were elevated following TH. A sharp peak in IL-10 levels was observed at 2 h after the insult. Kupffer cell (KC) depletion prior to TH reduced plasma IL-6, IL-10 and TNF-alpha levels, whereas treatment with anti-IL-10 after TH increased IL-6 and TNF-alpha levels. Kupffer cell mRNA expression for IL-6, IL-10 and TNF-alpha was elevated in the TH group and further increased by anti-IL-10 treatment. These findings indicate that KC-dependent IL-10 regulates the early systemic inflammatory response after TH. Thus, while IL-10 is an important mediator of immunosuppression following traumatic injury, it also is beneficial with regard to its ability to counter-regulate the early inflammatory response under such conditions.
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, G094 Volker Hall, 1670 University Blvd., Birmingham, AL 35294-0019, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schneider
authors.forename: Martin G
authors.initials: MG
authors.lastname: Schwacha
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006470:Hemorrhage / Q000097:blood* / Q000150:complications / Q000473:pathology*; D018836:Inflammation Mediators / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007728:Kupffer Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D053701:Receptors, Interleukin-10; D012097:Repressor Proteins / Q000235:genetics; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics; D014947:Wounds and Injuries / Q000097:blood* / Q000150:complications / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10