Effect of n-acetyl-l-cysteine on cytokine production by human peripheral blood mononuclear cells

Objectives: This study investigates the in vitro effect of the antioxidant drug, N-acetyl-L-cysteine (NAC), on cytokine production by peripheral blood mononuclear cells (PBMC). Methods: PBMC were isolated by Ficoll-Hypaque, and stimulated with anti-CD3 antibodies, phytohaemagglutinin (PHA), lipopolysaccharide (LPS) for 24 hours in the presence or absence of 5 mM NAC. The cytokines produced were measured by enzyme-linked immunosorbent assay (ELISA). Results: Treatment with NAC significantly up-regulates the secretion of IL-1β, IL-5 (interleukin) and IFN-γ (interferon) and down regulates IL-10 production, after anti-CD3 or PHA (p<0.05), but not after LPS stimulation. NAC also significantly increased total IL-12 secretion after anti-CD3 (but not PHA or LPS) stimulation and IL-12p40 after anti-CD3, PHA, and LPS stimulation (p <0.05). Conclusion: These results indicate that NAC up-regulated the production of pro-inflammatory cytokines, and down regulated anti-inflammatory cytokine production by PBMC, in a process which may be associated with increased levels of glutathione (GSH). Further work is required to determine whether this increase or decrease in cytokine production is due to direct effect of NAC.