Short-term adolescent nicotine exposure in rats elicits immediate and delayed deficits in T-lymphocyte function: Critical periods, patterns of exposure, dose thresholds

摘要

Prenatal nicotine exposure elicits lasting deficiencies in T-lymphocyte mitogenesis, and the period of vulnerability extends into adolescence, the stage at which smoking typically commences. We explored the importance of nicotine exposure patterns (continuous infusion vs. repeated subcutaneous injections), dose-effect relationships, and specificity of the effects. Adolescent rats were given nicotine infusions for 1 week beginning on postnatal day (PN) 30, using a regimen (6mg/kg/day) that produces plasma nicotine levels (25ng/ml) similar to those in smokers; another group received 2 mg/kg/day. At the end of the infusion period (PN37), T-lymphocyte mitogenic responses to concanavalin A were deficient in the group receiving 6mg/kg/day; values for the2mg/kg/day group were intermediate between controls and the 6mg/kg/day group. One week after the termination of nicotine treatment, responses returned to normal, only to reemerge in young adulthood (PN65), at which stage adverse effects were significanteven for the group that received 2mg/kg/day. In contrast to the T-cell alterations, B-lymphocyte responses were unaffected. Administering the same total doses of nicotine by twice-daily subcutaneous injections over the 1-week treatment period (1 or 3 mg/kg per injection) did not evoke deficits in responses of cither T-cells or B-cells, even though the high dose produced overt systemic toxicity and persistent weight loss. Our results indicate that adolescent nicotine exposure, even at levels below thoseassociated with active smoking, elicits selective deficits in T-lymphocyte function. Although short-term adaptations may correct the effects, deficits reemerge in young adulthood despite cessation of nicotine exposure.