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.


OBJECTIVE
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 microgram of toxin A or 3 micrograms of okadaic acid administered before or after injection of 0.1 microgram 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.


CONCLUSIONS
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.
Johansson
E
E
Department of Medical Microbiology and Immunology, University of Gothenburg, Sweden.
Jennische
E
E
Lange
S
S
Lönnroth
I
I
D000818:Animals; D000930:Antidiarrheals / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000009:adverse effects*; D016360:Clostridioides difficile; D004768:Enterotoxins / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000009:adverse effects; D007275:Injections, Intravenous; D007419:Intestinal Secretions / Q000187:drug effects; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008026:Ligation; D008297:Male; D009479:Neuropeptides / Q000627:therapeutic use*; D019319:Okadaic Acid / Q000009:adverse effects*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use
D000930:Antidiarrheals; D001427:Bacterial Toxins; D004768:Enterotoxins; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D011994:Recombinant Proteins; C049628:antisecretory factor; C041348:tcdA protein, Clostridium difficile; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases