Chronic self-administration of nicotine in rats impairs T cell responsiveness.
Chronic exposure of rodents to nicotine via subcutaneously or intracerebroventricularly implanted miniosmotic pumps affects T cell function. However, this method of continuous nicotine administration does not replicate the self-motivated administration of nicotine in human smokers. To determine whether nicotine impairs the immune system under conditions pertinent to human smokers, we investigated the T cell responsiveness of male Lewis rats self-administering (SA) nicotine (0.03 mg/kg of body weight per injection) 40 to 50 times/day for 5 weeks, using a model of virtually unlimited access to nicotine. Compared with sham control animals, the concanavalin A-induced proliferation of spleen cells from SA rats was significantly decreased. Moreover, the ability of spleen cells to mobilize intracellular Ca(2+) after ligation of the T cell antigen receptor (TCR) with an anti-alphabeta TCR antibody was significantly less in SA than in control rats. In addition, inositol 1,4,5-trisphosphate (IP(3))-sensitive intracellular Ca(2+) stores were markedly depleted in spleen cells from SA animals. These results suggest that chronic nicotine self-administration suppresses T cell responsiveness, and this suppression may result from an impaired TCR-mediated signaling that stems from the depletion of IP(3)-sensitive intracellular Ca(2+) stores.
Immunology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Road SE, Albuquerque, NM 87108, USA.
Roma
R
Kalra
Shashi P
SP
Singh
Dean
D
Kracko
Shannon G
SG
Matta
Burt M
BM
Sharp
Mohan L
ML
Sopori
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003367:Cotinine / Q000097:blood; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D012646:Self Administration; D012907:Smoking / Q000473:pathology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*
D018722:Nicotinic Agonists; D011948:Receptors, Antigen, T-Cell; D003208:Concanavalin A; D009538:Nicotine; D015544:Inositol 1,4,5-Trisphosphate; D003367:Cotinine