Inflammatory bowel disease is characterized by chronic
inflammation of the intestine and is accompanied by damage of the epithelial lining and by undesired immune responses towards enteric bacteria. It has been demonstrated that intestinal
alkaline phosphatase (iAP) protects against the induction of
inflammation, possibly due to dephosphorylation of
lipopolysaccharide (LPS). The present study investigated the therapeutic potential of iAP in intestinal
inflammation and epithelial damage. Intestinal epithelial damage was induced in C57BL/6 mice using detran
sulfate sodium (DSS) and iAP was administered 4days after initial DSS exposure. Loss in
body weight was significantly less in iAP-treated mice and accompanied with reduced colon damage (determined by combination of crypt loss, loss of goblet cells, oedema and infiltrations of neutrophils). Treatment with iAP was more effective in case of severe
inflammation compared to situations of mild to moderate
inflammation.
Rectal administration of LPS into a moderate inflamed colon did not aggravate
inflammation. Furthermore, soluble iAP did not lower LPS-induced
nuclear factor-kappaB activation in epithelial cells in vitro but induction of cellular AP expression by
butyrate resulted in decreased LPS response. In conclusion, the present study shows that oral iAP administration has beneficial effects in situations of severe intestinal epithelial damage, whereas in moderate
inflammation endogenous iAP may be sufficient to counteract disease-aggravating effects of LPS. An approach including iAP treatment holds a therapeutic promise in case of severe
inflammatory bowel disease.