Interleukin-1 and experimental gastric ulcer healing in the rat

The involvement of inflammation in peptic ulcer development and healing attracts growing interest. Since lymphokines, in particular interleukin-1 (IL-1), as ubiquitous mediators of inflammation are currently intensively studied in the gastrointestinal tract, we assessed the effect of this cytokine as well as that of a specific IL-1 release inhibitor (IX 207-887 (IX)) on development and healing of experimental gastric ulcers. After a single dose of IL-1, 4 micrograms/kg, i. p., basal acid secretion was almost completely inhibited for 4 hours in conscious chronic gastric fistula rats. In a first study, following induction of a 7 mm wide cryo-ulcer in the gastric corpus, three groups of 24 rats were treated either with a non-acid inhibitory dose of IL-1 (0.4 microgram/kg) or with an antisecretory regimen (4 micrograms/kg) b.i.d. or saline control. Ulcer size did not differ from that of control animals, neither after 24h nor 7 days. Similarly, IX applied daily (20 mg/kg/s.c) from 5 days before ulcer induction and continued thereafter for 15 days had no effect on ulcer development or healing. Despite its anti-inflammatory property IX produced no macroscopically visible damage on the gastric or intestinal mucosa and may therefore offer a higher safety profile within the gastrointestinal tract than conventional non-steroidal anti-inflammatory drugs.