Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis.

Abstract

Summary N-Acetyl-L-cysteine (NAC) is an antioxidant precursor of intracellular glutathione (GSH), usually given in humans as a mucolytic agent . In vitro, NAC and GSH have been shown to act on T cells by increasing interleukin (IL) 2 production, synthesis and turnover of IL-2 receptors, proliferation, cytotoxic properties, and resistance to apoptosis. We report here that NAC and GSH decrease in a dose-dependent manner human IL-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 y and increased IL-2 production and T cell proliferation . A functional consequence was the capacity ofNAC and GSH to selectively decrease in a dose-dependent manner IL-4-induced immunoglobulin (Ig) E and IgG4 production by human peripheral blood mononuclear cells . Interestingly, NAC and GSH also acted directly on purified tonsillar B cells by decreasing the mature e messenger RNA, hence decreasing IgE production . In contrast, IgA and IgM production were not affected . At the same time, B cell proliferation was increased in a dose-dependent manner. Not all antioxidants tested but only SH-bearing molecules mimicked these properties. Finally, when given orally to mice, NAC decreased both IgE and IgG1 antibody responses to ovalbumin. These results demonstrate that NAC, 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.

Mitochondrial Reactive Oxygen Species Control T Cell Activation by Regulating IL-2 and IL-4 Expression: Mechanism of Ciprofloxacin-Mediated Immunosuppression

“…Likewise, the treatment of primary human T cells with NAC efficiently attenuates IL-4 expression and secretion (47,48). Our work confirms these studies and extends the regulatory principle previously identified for CD95L to the transcriptional regulation of IL-2 and IL-4 genes.…”

Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation

“…In this regard, it is noteworthy that systemic administration of reagents that replenish GSH, such as NAC or 2-oxothiazolidine-4-carboxylic acid, has been shown to suppress Th2-type immune response, and to reduce airway inflammation and hyper-reactivity in animal models of asthma [40,41]. These results are in line with our present results that EDC that deplete intracellular GSH in APC promote Th2 polarization and that one EDC, TBT, exacerbates airway inflammation in a murine model of asthma.…”

Oxidative stress and regulation of glutathione in lung inflammation

“…Intracellular redox GSH levels in these immune/inflammatory cells may also effect signal transduction and activation of transcription factors and lead to elevated gene expression (e.g. of IL-8 and IL-4) [8,234]. GSH deficiency also leads to T-cell inactivation and apoptosis [235,236].…”