Reduction of aspirin-induced gastric damage in rats by interleukin-1 beta: possible involvement of endogenous corticosteroids.
Administration of interleukin-1 (IL-1; 0.01-3 microgram/kg) by either i.p. or intragastric routes to rats reduced aspirin-induced gastric damage. These effects of IL-1 were not subject to desensitization by its pretreatment and were obtained without modification of the acute anti-inflammatory efficacy of aspirin. Gastroprotection could be effected without major modification of gastric tissue to form prostaglandins I2 or E2. A dose-related decrease of the acidic gastric fluid secretion induced by aspirin was observed with i.p. administered IL-1 was found to reduce gastric fluid volume only at the highest dose tested, although this was not associated with increased gastroprotection. By using adrenalectomized rats the gastric damage induced by aspirin was increased approximately 3-fold. IL-1 treatment, albeit with higher dosage, again reduced lesion formation. Treatment of adrenalectomized rats with dexamethasone and IL-1 synergistically reduced the gastric damage caused by aspirin. In normal rats these treatments caused only an additive reduction of lesion formation although the presence of endogenous glucocorticoid in these animals may mask any effects of the exogenously administered dexamethasone. The glucocorticoid-receptor antagonist, RU 38486, also potentiated aspirin-induced gastric damage and reduced the gastroprotective efficacy of IL-1 without modifying its effect on gastric fluid volume. The data indicate that gastroprotective actions of IL-1 are unlikely to be related upon effects on prostaglandin synthesis or gastric secretion. Endogenous glucocorticoids appear to have a modulatory role in controlling the severity of gastric damage evoked by aspirin and may potentiate the protective actions of IL-1.
Perretti
M
M
Sclavo Research Centre, Laboratory of Pharmacology, Siena, Italy.
Mugridge
K G
KG
Wallace
J L
JL
Parente
L
L
D000315:Adrenalectomy; D000818:Animals; D001241:Aspirin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003907:Dexamethasone / Q000627:therapeutic use; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced; D011464:Epoprostenol / Q000096:biosynthesis; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control
D007375:Interleukin-1; D003907:Dexamethasone; D011464:Epoprostenol; D015232:Dinoprostone; D001241:Aspirin