Souza, D.G., Guabiraba Brito, R., Pinho, V., Bristow, A., Poole, S. and Teixeira, M.M. (2003) IL-1-driven endogenous IL-10 production protects against the systemic and local acute inflammatory response following intestinal reperfusion injury. Journal of Immunology, 170(9), pp. 4759-4766.
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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, demons strating 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Guabiraba Brito, Dr Rodrigo |
| Authors: | Souza, D.G., Guabiraba Brito, R., Pinho, V., Bristow, A., Poole, S., and Teixeira, M.M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Immunology |
| ISSN: | 0022-1767 |
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