Neuroimmunological effects of exposure to methylmercury forms in the Sprague-Dawley rats. Activation of the hypothalamic-pituitary-adrenal axis and lymphocyte responsiveness.
The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 micrograms per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte prolife ration after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of (MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.
Ortega
H G
HG
Clinical Immunology and Allergy Section, Tulane University Medical School, New Orleans, Louisiana 70112, USA. hortega@mailhost.tcs.tulane.edu
Lopez
M
M
Takaki
A
A
Huang
Q H
QH
Arimura
A
A
Salvaggio
J E
JE
D000284:Administration, Oral; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D007107:Immune System / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D009490:Neurosecretory Systems / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D008767:Methylmercury Compounds; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone