Arginine analogues suppress antigen-specific and -nonspecific T lymphocyte proliferation

Using analogues of arginine to inhibit nitric oxide (NO.) production, investigators have demonstrated the intermediary role of NO. in a variety of physiological events including the antimicrobial activity exhibited by macrophages in vitro. In an effort to establish the effector function of NO. in the antimicrobial activity expressed by macrophages in vivo, several groups report treating infected animals with relatively high concentrations of these same analogues. In the present study, we found that the arginine analogues NG-monomethyl-L-arginine, N omega-nitro-L-arginine methyl ester, aminoguanidine, and L-canavanine at concentrations > or = 10 mM significantly inhibited both the antigen-specific and -nonspecific proliferation of T lymphocytes in culture. These findings indicate that in vivo experiments demonstrating the suppressive effect of arginine analogues on host defenses are subject to alternative interpretations that do not directly involve the microbicidal activity of macrophages.