The translocation of enteric bacteria and the potential role of these organisms or their antigenic/phlogistic metabolites in the etiology of multisystem organ failure (MOF) have drawn attention to the mucosal immune system (MIS) as a possibly defective component of the """"""""mucosal barrier"""""""" in the intestine and, as such, a contributor to MOF. The long- term objective is to determine if immunosuppression or anergy in the intestine, resulting from trauma to the gastrointestinal (GI) tract, can be alleviated through nutritional means. The hypothesis will be tested that specific nutrients preserve infection-related immunity in the intestine of rats traumatized by irradiation and/or enhance the restoration of immunity, once reduced. There are two specific aims.
Specific Aim #1 is: To determine the ability of enterally administered amino acids (arginine, glutamine, ornithine) to protect rats from loss of mucosal immune responsiveness in the intestine caused by exposure to low-dose gamma rays delivered as total abdominal irradiation (TAI).
Specific Aim #2 is: To determine the relative ability of enterally and parenterally administered amino acids to enhance the restoration of mucosal immune responsiveness once suppressed by TAI. Irradiation is an extrinsic stimulus to which the GI tract is particularly sensitive, is a relevant environmental hazard to humans, and can be precisely controlled in the laboratory to systematically assess potentially adverse consequences on the MIS. The rationale for studying nutrients as potential immunoprotectants is that enteral nutritional support, employed early after trauma, purportedly preserves the integrity of the mucosal barrier. The protective effects of glutamine and ornithine will be compared relative to that of arginine. Prospects for preventing or restoring trauma-induced defects in the MIS are compromised by an inadequate knowledge of the physiology of the MIS and by a lack of methods to quantify preventive or restorative procedures. These impediments are obviated in a host-parasite model to be employed to accomplish the two specific aims. In this model, effects of perturbations on immune responsiveness caused by gamma radiation from a cobalt-60 source will be quantified by measurement of electrophysiological correlates of anaphylaxis-mediated epithelial CI- secretion evoked by parasite-derived antigen and by direct measurement of parasite infectivity, i.e., measurement of acquired resistance to reinfection.
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