Gastric cytoprotection by intracisternal interleukin-1 beta in the rat.
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.
Robert
A
A
Safety Pharmacology, Upjohn Company, Kalamazoo, MI.
Saperas
E
E
Zhang
W R
WR
Olafsson
A S
AS
Lancaster
C
C
Tracey
D E
DE
Chosay
J G
JG
Taché
Y
Y
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007267:Injections; D007278:Injections, Spinal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013270:Stomach / Q000187:drug effects / Q000473:pathology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D000431:Ethanol; D007213:Indomethacin