REACTIVE OXYGEN METABOLITES IN PIGLET CRYPTOSPORIDIOSIS

Piglet cryptosporidiosis is characterized by intestinal villous damage and malabsorption, and by reduced NaCl absorption in response to pros taglandins (PGs), which act directly on the epithelium and indirectly through enteric nerves. We hypothesized that phagocyte-derived reactiv e oxygen metabolite (ROM) production contributed to PG synthesis and a ltered transport in inflamed ileum. Ileal mucosa from control and infe cted piglets was analyzed for villous height, PGE(2), catalase (an end ogenous antioxidant), and malondialdehyde (MDA, a by-product of lipid peroxidation) from d 2-8 after infection. The response of control ilea l mucosa to exogenous ROM and infected mucosa to antioxidant treatment was also studied in tissues mounted in Ussing chambers. Increased lev els of MDA on d 2 preceded increased PGE(2) on d 3-4, which correlated with the acute diarrheal phase; however the most severe villous atrop hy (d 8) correlated with the highest levels of catalase and MDA but lo w levels of PGE(2). Control mucosa responded to H2O2 with indomethacin - and tetrodotoxin-sensitive transient increases in short circuit curr ent (I-sc), which were accompanied by increased tissue production of 6 -keto-PGF(1a), the stable metabolite of PGI(2); however, no increased PGE(2) production was detectable. A stable analog of PCI2, carbacyclin , mimicked the transient I-sc response to H2O2; however, several antio xidants failed to alter the abnormal I-sc of infected tissue, These re sults suggest that there is evidence of increased ROM production in cr yptosporidial infection and that intestinal PG synthesis and inhibited NaCl absorption may be mediated partially by ROM in this model. Addit ional, cooperative factors, such as PGE(2) production, however, are li kely needed to induce the alterations in ion transport seen in this in fection.