Subclinical doses of the nerve gas sarin impair T cell responses through the autonomic nervous system.
The nerve gas sarin is a potent cholinergic agent, and exposure to high doses may cause neurotoxicity and death. Subclinical exposures to sarin have been postulated to contribute to the Gulf War syndrome; however, the biological effects of subclinical exposure are largely unknown. In this communication, evidence shows that subclinical doses (0.2 and 0.4 mg/m(3)) of sarin administered by inhalation to F344 rats for 1 h/day for 5 or 10 days inhibited the anti-sheep red blood cell antibody-forming cell response of spleen cells without affecting the distribution of lymphocyte subpopulations in the spleen. Moreover, sarin suppressed T cell responses, including the concanavalin A (Con A) and the anti-alphabeta-T cell receptor (TCR) antibody-induced T cell proliferation and the rise in the intracellular calcium following TCR ligation. These concentrations of sarin altered regional but not total brain acetylcholinesterase activity. Interestingly, serum corticosterone levels of the sarin-treated animals were dramatically lower than the control animals, indicating that sarin-induced immunosuppression did not result from the activation of the hypothalamus-pituitary-adrenal (HPA) axis. Pretreatment of animals with the ganglionic blocker chlorisondamine abrogated the inhibitory effects of sarin on spleen cell proliferation in response to Con A and anti-TCR antibodies. These results suggest that the effects of sarin on T cell responsiveness are mediated via the autonomic nervous system and are independent of the HPA axis.
Kalra
Roma
R
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA.
Singh
Shashi P
SP
Razani-Boroujerdi
Seddigheh
S
Langley
Raymond J
RJ
Blackwell
Walter B
WB
Henderson
Rogene F
RF
Sopori
Mohan L
ML
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002714:Chlorisondamine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012524:Sarin / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D011948:Receptors, Antigen, T-Cell; D012524:Sarin; D002714:Chlorisondamine; D002118:Calcium; D003345:Corticosterone