Arginine, glutamine, and dehydroepiandrosterone reverse the immunosuppressive effect of prednisone during gut-derived sepsis

Objective Corticosteroids are used broadly in clinical practice but may profoundly impair resistance to infections. In contrast, arginine and glutamine are safe and effective immunonutrients that can improve resistance to infection in both animals and humans. This study assessed whether arginine and/or glutamine, with or without dehydroepiandrosterone, a natural endogenous steroid, could reverse the susceptibility to infection caused by prednisone in a burned animal model. Design Prospective, randomized study. Setting A laboratory approved by the American Association for the Accreditation of Laboratory Animal Care at the Shriners Burns Institute, Cincinnati Unit. Subjects Adult female Balb/c mice, weighing 18 to 22 g. Interventions Animals were prefed an arginine- and/or glutamine- or a glycine-supplemented diet for 14 days. Dehydroepiandrosterone (25 mg/kg/day) and/or prednisone (10 mg/kg/day) were given on days -4 to 0 before animals were given a gavage of 109111 indium-oxine-radiolabeled or -unlabeled Escherichia coli and 20% total body surface area burn injury. Survival rate and the extent of translocation of E. coli were determined. Measurements and Main Results Feeding with diets supplemented with arginine, glutamine, and arginine plus glutamine and treatment with dehydroepiandrosterone reversed the susceptibility to infections caused by prednisone and burn injury. The beneficial effects were mediated by enhanced killing of translocated bacteria and/or by an improved gut barrier function. Conclusions Dietary supplementation can reverse the susceptibility to infections caused by prednisone. Both arginine and glutamine as well as dehydroepiandrosterone may be useful therapeutic agents for preventing infections in steroid-treated patients. (Crit Care Med 1997; 25:1207-1214)