Gastric cytoprotection by intracisternal interleukin-1 beta in the rat |
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Authors: | A Robert E Saperas W R Zhang A S Olafsson C Lancaster D E Tracey J G Chosay Y Taché |
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Affiliation: | Safety Pharmacology, Upjohn Company, Kalamazoo, MI. |
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Abstract: | The effects of intracisternal (ic) injection of recombinant interleukin-1 beta (IL-1) on absolute ethanol-induced gastric necrotic lesions were studied in conscious rats. IL-1 given ic inhibited ethanol-induced gastric lesions. The cytoprotective effect was dose dependent (ED175 ng/rat), long lasting with a maximal action when given 1-3 h prior to ethanol, blocked by ic injection of a IL-1 receptor antagonist protein (IRAP), and by intraperitoneal injection of indomethacin. IL-1, injected ic, was detected in the peripheral blood. However, IL-1 serum levels were lower after IL-1 injection ic than after ip at a dose giving equal gastric protection. These data show that ic IL-1 induces long lasting gastric protection mediated by interaction with IL-1 receptors and prostaglandin pathways at central and/or peripheral sites that remain to be localized. |
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