Antisecretory factor suppresses intestinal inflammation and hypersecretion

Background-Antisecretory factor (AF) is a recently identified regulatory protein which inhibits the intestinal fluid secretion induced by cholera toxin. Aims-To test the effect of AF on: (a) inflammation and hypersecretion induced by toxin A from Clostridium difficile; and (b) morphological changes and hypersecretion induced by okadaic acid (the blue mussel toxin) in rat intestinal mucosa. Methods-Morphological changes and fluid accumulation were observed in intestinal loops challenged with 1 mu g of toxin A or 3 mu g of okadaic acid administered before or after injection of 0.1 mu g of recombinant AF (rAF). Results-The cytotoxic and inflammatory reaction caused by toxin A was abolished after treatment with rAF given either intraveneously or intraluminally prior to the toxin or one hour after the toxin. The intestinal fluid response induced by toxin A and okadaic acid was reduced 55-80% by rAF. However, the characteristic increase in goblet cells at the tips of villi in the okadaic acid treated mucosa was not inhibited by rAF. Conclusion-Results suggest that AF might be involved in protection against inflammation and in counteracting dehydration caused by enterotoxins. Both effects are probably mediated via the enteric nervous system.