Chronic methamphetamine exposure alters immune function in normal and retrovirus-infected mice.
Methamphetamine (MA) abuse represents a growing problem in the USA with an increase of sudden death. To evaluate the immune function alterations due to chronic methamphetamine use, we examined C57BL/C mice with LP-BM5 retrovirus infection plus methamphetamine exposure. Mice were randomly assigned to the following groups: placebo, placebo retrovirus-infected, uninfected MA treated and retrovirus-infected MA treated. Placebo, MA-treated groups were intraperitoneally injected with saline, MA, respectively, with a gradually increasing dose from 15 to 40 mg/kg for 12 weeks (5 days/week). Con A- and LPS-induced mitogenesis of splenocytes, cytokine production by splenocytes culture and lipid peroxides in the liver were measured. Heart tissue histopathology was analyzed in all the groups with murine cytomegalovirus (CMV) superinfection. Our data showed that MA treatment significantly decreased production of IL-2 and interferon gamma (IFN-gamma) in uninfected mice but did not further suppress the reduced Th1 cytokines in retrovirus-infected mice. There were no significant effects on cytokines IL-4 and IL-6. However, tumor necrosis factor (TNF-alpha) was significantly increased in both uninfected and infected mice due to MA treatment. Lipid peroxides in liver were significantly increased both in uninfected and retrovirus-infected mice due to MA exposure. Vitamin E levels in liver were significantly decreased in uninfected mice due to MA treatment. CMV superinfection greatly increased the cardiac lesions in retrovirus-infected mice while no significant histopathology changes were detected due to MA treatment. Our data suggest that MA has immunomodulation activity, suppressing Th1 cytokine production and enhancing some Th2 cytokine secretion, as well as increasing lipid peroxides in uninfected mice. The interaction between LP-BM5 and MA remains unclear.
Yu
Qianli
Q
College of Public Health and School of Medicine, University of Arizona, Tucson 85724, USA.
Zhang
Dongqin
D
Walston
Michael
M
Zhang
Jin
J
Liu
Yingyin
Y
Watson
Ronald R
RR
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D007107:Immune System / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D008694:Methamphetamine