Central injection of nicotine increases hepatic and splenic interleukin 6 (IL-6) mRNA expression and plasma IL-6 levels in mice: involvement of the peripheral sympathetic nervous system

Accumulating evidence suggests that plasma levels of interleukin 6 (IL-6), a major cytokine stimulating the synthesis of acute-phase proteins, are int imately regulated by the central nervous system. Nicotine, one of the major drugs abused by humans, has been shown to affect immunological functions. In the present study, effects of intracerebroventricular (i.c.v.) injection of nicotine on plasma IL-6 levels were investigated in mice. Nicotine admi nistered i.c.v. dose-dependently increased plasma IL-6 levels; the lowest e ffective dose was 0.3 ng/mouse and the maximal effect was attained with the dose of 105 ng/mouse. The nicotine (105 ng/mouse, i.c.v.)-induced plasma I L-6 levels peaked at 3 h and approached basal levels 6 h after injection. M ecamylamine, a nicotinic receptor antagonist, blocked nicotine-induced plas ma IL-6 levels. Depletion of peripheral norepinephrine with 6-hydroxydopami ne [100 mg/kg, intraperitoneal (i.p.)] inhibited the nicotine-induced plasm a IL 6 levels by 57%, whereas central norepinephrine depletion with 6-hydro xydopamine (50 mu g/mouse, i.c.v.) had no effect. Pretreatment with prazosi n (alpha(1)-adrenergic antagonist; 1 mg/kg, i.p.), yohimbine (alpha(2)-adre nergic antagonist; 1 mg/kg, i.p.), and ICI-118,551 (beta(2)-adrenergic anta gonist; 2 mg/kg, i.p.), but not with betaxolol (beta(1)-adrenergic antagoni st; 2 mg/kg, i.p.), inhibited nicotine-induced plasma IL-6 levels. Among th e peripheral organs, including the pituitary, adrenals, heart, lung, liver, spleen, and lymph nodes, nicotine (105 ng/mouse, i.c.v.) increased IL-6 mR NA expression only in the liver and spleen, which was inhibited by peripher al norepinephrine depletion. These results suggest that stimulation of cent ral nicotinic receptors induces plasma IL-6 levels and IL-6 mRNA expression in the liver and spleen via the peripheral sympathetic nervous system, alp ha(1)-, alpha(2)-, and beta(2)-adrenoreceptors being involved.