TY - JOUR
T1 - Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse
AU - Mata, Mariana M.
AU - Napier, T. Celeste
AU - Graves, Steven M.
AU - Mahmood, Fareeha
AU - Raeisi, Shohreh
AU - Baum, Linda L.
N1 - Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/4/5
Y1 - 2015/4/5
N2 - The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last operant session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4+, CD8+, CD200+ and CD11b/c+ lymphocytes in the spleen. Rats that self-administered methamphetamine had a lower frequency of CD4+ T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4+ T cells. Methamphetamine using rats had a higher frequency of CD8+ T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Our data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection.
AB - The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last operant session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4+, CD8+, CD200+ and CD11b/c+ lymphocytes in the spleen. Rats that self-administered methamphetamine had a lower frequency of CD4+ T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4+ T cells. Methamphetamine using rats had a higher frequency of CD8+ T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Our data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection.
KW - CD4 Tcells
KW - Inflammatory cytokines
KW - Methamphetamine
KW - Rat
KW - Self-administration
UR - http://www.scopus.com/inward/record.url?scp=84923618810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923618810&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2015.02.002
DO - 10.1016/j.ejphar.2015.02.002
M3 - Article
C2 - 25678251
AN - SCOPUS:84923618810
SN - 0014-2999
VL - 752
SP - 26
EP - 33
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -