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.


METHODS
Prospective, randomized study.


METHODS
A laboratory approved by the American Association for the Accreditation of Laboratory Animal Care at the Shriners Burns Institute, Cincinnati Unit.


METHODS
Adult female Balb/c mice, weighing 18 to 22 g.


METHODS
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 10(9) 111indium-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.


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.
Gennari
R
R
Department of Surgery, University of Cincinnati College of Medicine and Shriners Burn Institute, OH 45267-0558, USA.
Alexander
J W
JW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D018988:Bacterial Translocation; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011241:Prednisone / Q000494:pharmacology; D011446:Prospective Studies; D011897:Random Allocation; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D005973:Glutamine; D003687:Dehydroepiandrosterone; D001120:Arginine; D011241:Prednisone