Neonatal chlorpyrifos administration elicits deficits in immune function in adulthood: a neural effect?
Neural input plays a key role in the establishment of immune function, and environmental agents or drugs that interfere with the development of the nervous system elicit corresponding immunologic deficits. In the current study, we gave neonatal rats the widely used organophosphate pesticide, chlorpyrifos (CPF), and determined the immediate and long-term effects on T-lymphocyte function. Exposure of neonatal rats to 1 mg/kg of CPF daily on postnatal days (PN) 1-4 had no immediate effect (PN5) on T-cell mitogenic responses to concanavalin A challenge. However, once the animals reached adulthood, T-cell responses were significantly impaired. There were no deficits in basal T-cell replication rates, implying that the adverse effect of CPF exposure was specific to mitogenic activation. Treatment during a later neonatal period (PN11-14) elicited similar deficits in adulthood. CPF administration leads to inhibition of cholinesterase, and a cholinergic connection is supported by the fact that the results seen here correspond to those seen with a direct cholinergic stimulant (nicotine) administered during gestation or adolescence. These results indicate that exposure to CPF during a developmental period in which this organophosphate pesticide is known to produce lasting changes in neural function, elicits corresponding, long-term deficits in immune competence.
Navarro
H A
HA
Center for Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC 27709, USA.
Basta
P V
PV
Seidler
F J
FJ
Slotkin
T A
TA
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007107:Immune System / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D008934:Mitogens / Q000494:pharmacology; D009420:Nervous System / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D015213:Neuroimmunomodulation / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D008934:Mitogens; D003208:Concanavalin A; D004390:Chlorpyrifos