EFFECTS OF L-ARGININE SUPPLEMENTATION ON HUMAN LYMPHOCYTE-PROLIFERATION IN RESPONSE TO NONSPECIFIC AND ALLOANTIGENIC STIMULATION

Background: L-Arginine has been described as a potential immunostimula nt in vitro and in vivo. Excessive arginine, however, may be counterpr oductive. Data support the concept of minimal arginine requirements fo r normal lymphocyte proliferation, but the results of supplementation with pharmacologic doses of arginine have been contradictory. We hypot hesized that excessive arginine supplementation might result in a blun ting of normal immune responses of human lymphocytes in vitro. Materia ls and Methods: Peripheral blood mononuclear and T-cells were isolated from normal human donors. Cells were cultured in complete media with various concentrations of L-arginine, L-ornithine, and glycine. Lympho cytes were then stimulated with PHA or alloantigens, and proliferation was determined by measuring [H-3]thymidine incorporation. Results: Ly mphocyte proliferation was inhibited by L-arginine at pharmacologic do ses. The effects were completely reversible. This inhibition could not be prevented by lymphocyte stimulation with IL-2. Lymphocyte prolifer ation was more sensitive to inhibition by lower doses of arginine when alloantigens from irradiated fresh tumor cells or allogeneic lymphocy tes were the stimuli. Finally, lymphocytes showed variable sensitivity to inhibition of proliferation in response to mitogen when treated wi th L-ornithine (little to no effect) or L-arginine (consistent inhibit ion at high doses). Pharmacologic doses of L-arginine result in revers ible inhibition of normal lymphocyte proliferation in response to both mitogen and alloantigen. This inhibition could not be blocked by inte rleukin-2. Conclusions: We conclude that caution should be exercised w hen recommending aggressive L-arginine supplementation as a possible m ethod to reverse clinical immunosuppression caused by cancer, malnutri tion, or trauma. (C) 1997 Academic Press.