Possible factors involved in the protective effects of interleukin-1 in aspirin- and indomethacin-induced gastric damage

Interleukin-1 (IL-1) is a polypeptide cytokine that has been described as possessing a wide variety of immunogenic and non-immunogenic activities [1]. Recently another important facet of this cytokine’s biological activity has emerged concerning its protective effects against gastroduodenal damage in several animal models. This was first shown in the studies of Wallace et al. [2] which demonstrated IL-1 to potently reduce the gastric damage caused in rats by indomethacin and ethanol as well as the duodenal damage caused by the noxic agent cysteamine. Subsequent studies by Robert et al. [3] confirmed the cytokine’s protective effects in the ethanol model and also showed IL-1 to reduce the gastric damage caused by another non-steroidal anti-inflammatory drug (NSAID), aspirin. However, the mechanisms underlying the protective actions of IL-1 are not entirely clear. The cytokine is a potent stimulator of prostaglandin (PG) synthesis in many cell types [4–6] including rat forestomach [7] and rabbit colon [8]. The later study by Robert et al. [3] also indicated that administration of IL-1 to rats could increase the capacity of the gastric mucosa to synthesize PGE2. Since a number of PGs have the ability to protect the upper gastrointestinal tract [9] it is feasible that their increased synthesis caused by IL-1 may contribute to the reduced mucosal injury. Another factor which may contribute towards the gastroprotective actions of IL-1 is its ability to potently inhibit gastric acid secretion [2,3,10-15].