TUMOR-NECROSIS-FACTOR-ALPHA CHANGES PORCINE INTESTINAL ION-TRANSPORT THROUGH A PARACRINE MECHANISM INVOLVING PROSTAGLANDINS

Prostaglandins stimulate electrogenic anion secretion and inhibit sodi um chloride absorption in cryptosporidium induced pig diarrhoea. Becau se tumour necrosis factor alpha: (TNF alpha) is an early mediator of i nflammation and stimulates prostaglandin secretion, we investigated it s effect on intestinal ion transport. Cryptosporidium infected pig ile um showed higher macrophage infiltration and tissue TNF alpha-like act ivity than uninfected tissues (p<0.05, n=4 and p<0.05, n=12, respectiv ely). TNF alpha treatment of control porcine heal mucosa increased the short circuit current (Isc), a measurement of net anion secretion in this model (p<0.001, n=23). This effect was blocked by 10(-6) M indome thacin and Cl- replacement. Neither acute treatment nor preincubation of colonic intestinal epithelial cell monolayers (T84) with TNF alpha stimulated the Isc. However, co-mounting of TNF alpha preincubated pig jejunal fibroblasts (P2JF) monolayers back to back with untreated T84 monolayers dose-dependently induced an indomethacin sensitive increas e in Isc compared with values in untreated co-mounted monolayers (p<0. 001, n=11). These data suggest that in infectious diarrhoea, TNF alpha may induce Cl- secretion through a paracrine mechanism involving pros taglandin release from subepithelial cells, for example fibroblasts.