THIOLS DECREASE HUMAN INTERLEUKIN (IL)4 PRODUCTION AND IL-4-INDUCED IMMUNOGLOBULIN-SYNTHESIS

N-Acetyl-L-cysteine (NAG) is an antioxidant precursor oi intracellular glutathione (GSH), usually given in humans as a mucolytic agent. In v itro, NAC and GSH have been shown to act on T cells by increasing inte rleukin (IL) 2 production, synthesis and turnover of IL-2 receptors, p roliferation, cytotoxic properties, and resistance to apoptosis. We re port here that NAC and GSH decrease in a dose-dependent manner human I L-4 production by stimulated peripheral blood T cells and by T helper (Th) 0- and Th2-like T cell clones. This effect was associated with a decrease in IL-4 messenger RNA transcription. In contrast, NAC and GSH had no effect on interferon gamma and increased IL-2 production and T cell proliferation. A functional consequence was the capacity of NAC and GSH to selectively decrease in a dose-dependent manner IL-4-induce d immunoglobulin (Ig) E and IgG4 production by human peripheral blood mononuclear cells. Interestingly, NAC and GSH also acted directly on p urified tonsillar B cells by decreasing the mature epsilon messenger R NA, hence decreasing IgE production. In contrast, IgA and IgM producti on were not affected. At the same time, B cell proliferation was incre ased in a dose-dependent manner. Not all antioxidants tested but only SH-bearing molecules mimicked these properties. Finally, when given or ally to mice, NAC decreased both IgE and IgG1 antibody responses to ov albumin. These results demonstrate that NAG, GSH, and other thiols may control the production of both the Th2-derived cytokine IL-4 and IL-4 -induced Ig in vitro and in vivo.