Arginine Immunonutrition in Critically Ill Patients: A Clinical Dilemma

Joyce K. Stechmiller, PhD, ARNP; Beverly Childress, MSN; Tricia Porter, BSN


Am J Crit Care. 2004;13(1) 

In This Article

Arginine and the Immune System

Strong evidence[33,34] suggests that dietary supplementation with arginine enhances immunocompetence in adults in humans and in animal models. Dietary L-arginine modulates the activities of immune cells in several ways.[35,36] For example, dietary arginine can increase the weight of the thymus in healthy animals, an effect that is directly correlated with an increase in the number of thymic T lymphocytes.[22] Intravenous infusion of arginine is also associated with an increase in the release of T cells from the thymus.[37] In addition, arginine has a direct effect on T-cell activity in vivo and in vitro.[38,39] In one study,[40] maximal proliferation of peripheral mononuclear blood cells occurred when the cells were cultured in medium containing 0.04 mM arginine. In another study,[41] athymic nude mice fed a diet supplemented with arginine had greater numbers of splenic T cells and a stronger delayed-type hypersensitivity reaction, a measure of T-cell function, than did control mice not fed arginine. In a study in humans,[38] subjects had an increase in mitogenic responses in T cells after a few days of arginine supplementation at 30 g/d. This increase persisted for 2 to 3 weeks.

Arginine-derived nitric oxide also plays a major role in inflammation and immunity,[42] affecting most immune cells, including T cells. At low doses, nitric oxide enhances T-cell mitogenesis; at higher doses, the effect is inhibitory.[40] Macrophages use L-arginine as a major substrate for many of their functions. In inflammation, macrophages are primarily responsible for the expression of iNOS.[43,44,45] Although the production of nitric oxide varies according to the nature of the stimulus, early release of the oxide is due to iNOS activity. Arginase expression occurs several hours later.[23] Although interleukin (IL)-4, IL-10, and prostaglandin E2 inhibit iNOS expression, they induce arginase expression. During a septic inflammatory response, competition between the functions of iNOS and arginase may occur, and as a result macrophages help organize cells and prioritize cellular responses. Macrophages also defend against growth, activity, and killing of bacteria and parasites by releasing nitric oxide.

Arginine also enhances phagocytosis by neutrophils and adhesion of polymorphonuclear cells, activities that help produce nitric oxide for immunomodulation. This enhancement is protective and is different from the cytotoxic response generated by macrophages that results in the production of superoxide.[46]


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