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Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, 200–702, South Korea
1Correspondence: Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, Kangwon-Do, 200–702, South Korea. E-mail: dksong{at}sun.hallym.ac.kr
Accumulating evidence suggests that plasma levels of interleukin 6
(IL-6), a major cytokine stimulating the synthesis of acute-phase
proteins, are intimately 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 administered i.c.v.
dose-dependently increased plasma IL-6 levels; the lowest effective
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
IL-6 levels peaked at 3 h and approached basal levels 6 h
after injection. Mecamylamine, a nicotinic receptor antagonist, blocked
nicotine-induced plasma IL-6 levels. Depletion of peripheral
norepinephrine with 6-hydroxydopamine [100 mg/kg, intraperitoneal
(i.p.)] inhibited the nicotine-induced plasma IL-6 levels by 57%,
whereas central norepinephrine depletion with 6-hydroxydopamine (50
µg/mouse, i.c.v.) had no effect. Pretreatment with prazosin
(
1-adrenergic antagonist; 1 mg/kg, i.p.), yohimbine
(2-adrenergic antagonist; 1 mg/kg, i.p.), and
ICI-118,551 (ß2-adrenergic antagonist; 2 mg/kg, i.p.),
but not with betaxolol (ß1-adrenergic antagonist; 2
mg/kg, i.p.), inhibited nicotine-induced plasma IL-6 levels. Among the
peripheral organs, including the pituitary, adrenals, heart, lung,
liver, spleen, and lymph nodes, nicotine (105 ng/mouse, i.c.v.)
increased IL-6 mRNA expression only in the liver and spleen, which was
inhibited by peripheral norepinephrine depletion. These results suggest
that stimulation of central nicotinic receptors induces plasma IL-6
levels and IL-6 mRNA expression in the liver and spleen via the
peripheral sympathetic nervous system, 1-,
2-, and ß2-adrenoreceptors being
involved.—Song, D.-K., Im, Y.-B., Jung, J.-S., Suh, H.-W., Huh, S.-O.,
Song, J.-H., Kim, Y.-H. 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.
Key Words: norepinephrine • sympathetic nervous system • liver • spleen
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