title: IL-1-driven endogenous IL-10 production protects against the systemic and local acute inflammatory response following intestinal reperfusion injury.
abstract: TNF-alpha release and action are central in the pathogenesis of the local and systemic inflammatory responses that occur after intestinal reperfusion. In this study we examined whether IL-1 participated in the cascade of events leading to TNF-alpha production and TNF-alpha-mediated injury following reperfusion of the ischemic superior mesenteric artery in rats. Blockade of the action of IL-1 by the use of anti-IL-1 antiserum or administration of IL-1R antagonist (IL-1ra), a natural antagonist of IL-1Rs, resulted in marked enhancement of reperfusion-associated tissue injury, TNF-alpha expression, and lethality. In contrast, there was marked decrease in IL-10 production. Facilitation of IL-1 action by administration of anti-IL-1ra, which antagonizes endogenous IL-1ra, or exogenous administration of rIL-1beta suppressed reperfusion-induced tissue pathology, TNF-alpha production, and lethality, but increased IL-10 production. Exogenous administration of IL-10 was effective in preventing the increase in tissue or plasma levels of TNF-alpha, the exacerbated tissue injury, and lethality. An opposite effect was observed after treatment with anti-IL-10, demonstrating a role for endogenous production of IL-10 in modulating exacerbated reperfusion-associated tissue pathology and lethality. Finally, pretreatment with anti-IL-10 reversed the protective effect of IL-1beta on reperfusion-associated lethality. Thus, IL-1 plays a major role in driving endogenous IL-10 production and protects against the TNF-alpha-dependent systemic and local acute inflammatory response following intestinal reperfusion injury.
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Souza
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Guabiraba
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pinho
authors.forename: Adrian
authors.initials: A
authors.lastname: Bristow
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000502:physiology / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000276:immunology / Q000473:pathology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10