TUMOR-NECROSIS-FACTOR DEPRESSES GUT ABSORPTIVE FUNCTION

Although recent studies have shown that gut absorptive function is sig nificantly depressed even in the early hyperdynamic phase of sepsis, t he mechanism responsible for this is unknown. Tumor necrosis factor (T NF-alpha) is a potent mediator of shock resulting in a marked inflamma tory response leading to mucosal erosions of the gut and multiple orga n failure. Although TNF is elevated in early sepsis, it remains unknow n whether TNF plays any role in the depression of gut absorptive funct ion under these conditions. To study this, we used the 1 hr D-xylose a bsorption test. C3H/HeN mice (n = 12) were lightly anesthetized, and a femoral artery and the portal vein were cannulated. After recovery fr om anesthesia, 125 mug recombinant murine TNF-alpha (rMuTNF-alpha)/kg body weight was given via the tail vein to one group of animals, while another group received an equivalent volume of saline (sham). One hou r later, D-xylose was given orally. The systemic blood pressure was re corded 1 hr thereafter and D-xylose concentration in a sample of porta l blood was determined colorimetrically. Results show that, while the systemic pressure was elevated 2 hr after administration of rMuTNF-alp ha, D-xylose absorption was severely depressed. Thus the depressed gut absorptive function seen in the early stage of sepsis may be mediated directly or indirectly by TNF-alpha.