Acute and chronic nicotine exposures modulate the immune system through different pathways

We have previously shown that T cells from rats exposed chronically to ciga rette smoke or nicotine (NT) exhibit T cell anergy and decreased proliferat ion to T cell mitogens. Effects of chronic NT on T cell function persist fo r at least 2 weeks after the termination of NT treatment. Moreover, these e ffects of NT are causally related to the decreased Ca2+ response to T cell receptor (TCR) ligation and constitutive activation of protein tyrosine kin ase (PTK) and phospholipase C (PLC)-gamma 1 activities. Acute NT treatment also suppresses the Con A-induced T cell proliferation; however, it is not known whether the mechanism(s) by which acute and chronic NT treatments inh ibit T cell proliferation are identical. To evaluate this question, LEW rat s were acutely treated with NT (1 mg/kg body wt) for 1, 2, or 24 h by an ip injection or implanted with constant-release miniosmotic pumps containing saline or NT (1 mg/kg body wt/day) for a 3-week chronic exposure. Inhibitio n of Con A-induced proliferation of peripheral brood cells (PBC) by both ac ute and chronic treatments was reversed by the inhibitor of nicotinic acety lcholine receptors, mecamylamine (MEC), indicating that these receptors are required for T cell proliferation. However, the effect of acute NT on the Con A response was short lived (i.e., observed at 1 and 2 h but not at 24 h after NT administration) and was seen in PBC but not in spleen cells. Unli ke the chronic treatment, acute NT administration neither suppressed signif icantly the TCR-mediated [Ca2+](i) response nor did it cause the constituti ve activation of PTK and PLC-gamma 1 activities in blood lymphocytes. Acute , but not chronic, NT administration increased the plasma corticosterone co ncentration, and this increase was also inhibited by MEC. Moreover, adrenal ectomy abrogated the acute but not chronic NT effects on the Con A response . Thus, the acute and chronic effects of NT on T lymphocytes are mechanisti cally distinct phenomena. Whereas chronic administration of NT causes T cel l anergy, acute effects are primarily mediated via the activation of the hy pothalamus-pituitary-adrenal axis. (C) 2000 Academic Press.