Short-term adolescent nicotine exposure in rats elicits immediate and delayed deficits in T-lymphocyte function: critical periods, patterns of exposure, dose thresholds.
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 (6 mg/kg/day) that produces plasma nicotine levels (25 ng/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 6 mg/kg/day; values for the 2 mg/kg/day group were intermediate between controls and the 6 mg/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 significant even for the group that received 2 mg/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 either 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 those associated 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.
Navarro
Hernán A
HA
Center for Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC, USA.
Basta
Patricia V
PV
Seidler
Frederic J
FJ
Slotkin
Theodore A
TA
D000293:Adolescent / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
D005731:Ganglionic Stimulants; D009538:Nicotine