Differential impact of nicotine on cellular proliferation and cytokine production by LPS-stimulated murine splenocytes

The immunoregulatory effects of nicotine have not been fully clarified and the reported data are often conflicting. The present study investigated the role of nicotine as an immunomodulator of murine splenocytes stimulated by lipopolysaccharide (LPS), the endotoxin component of gram-negative bacteri a. BALB/c female mice of two different ages, young (2-3 months) and old (18 -22 months), were used. The cells were incubated with nicotine at two diffe rent time points, 3 h pre-incubation and concurrent incubation relevant to LPS stimulation, before further incubation for 48 or 72 h. Treatment of mur ine splenocytes with nicotine showed an impact on cellular proliferation as well as on the production of the pro-inflammatory cytokines, tumor necrosi s factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The results indicated that nicotine significantly inhibited cellular proliferation of murine sple nocytes in a concentration-related manner (32, 64 and 128 mu g/ml). Timing of nicotine exposure prior to LPS stimulation was critical in terms of immu nological impact on cytokine production. TNF-alpha and IL-6 production were significantly enhanced by 1 mu g/ml of nicotine when cells were pre-incuba ted with nicotine for 3 h compared to concurrent incubation relative to LPS stimulation. The alteration in cytokine production varied with the age of the mouse. TNF-alpha production was significantly inhibited by nicotine in young mice, while IL-6 production was significantly inhibited by nicotine i n old mice. Since any immunomodulation that alters the profile of these cyt okines may cause an imbalance in the immune system impinging on health stat us, these findings may be important when dealing with the concept of nicoti ne as a therapeutic agent. (C) 2000 International Society for Immunopharmac ology. Published by Elsevier Science Ltd. All rights reserved.