Endotoxin protects the gastric mucosa against ulcerogenic stimuli

It is well-documented that large amounts of endotoxin produce hemorrhagic mucosal lesions in the stomach. To determine whether endotoxin, when injected at small doses, similarly exerts ulcerogenic actions, endotoxin (0.4-40 micrograms/kg) was injected into 24 hr-fasted rats. These small doses of endotoxin did not affect the integrity of the gastric mucosa. Unexpectedly, however, pretreatment with these minute amounts of endotoxin protected the gastric mucosa against various ulcerogenic stimuli such as stress, nonsteroidal anti-inflammatory drugs and ethanol. The anti-ulcer actions of endotoxin were not observed in endotoxin-insensitive animals (C3H/HeJ mice), thereby suggesting that endogenous cytokines such as interleukin-1 may mediate these protective actions. These findings stand in contrast to the toxic effect of endotoxin as an ulcerogen and indicate that endotoxin, albeit its term "toxin," may have a beneficial effect for the host.