title: Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse.
abstract: 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.
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, United States.
authors: Mariana M
authors: MM
authors: Mata
authors: Department of Pharmacology and Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, IL 60612, United States.
authors: T Celeste
authors: TC
authors: Napier
authors: Department of Pharmacology and Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, IL 60612, United States.
authors: Steven M
authors: SM
authors: Graves
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, United States.
authors: Fareeha
authors: F
authors: Mahmood
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, United States.
authors: Shohreh
authors: S
authors: Raeisi
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, United States. Electronic address: Linda_L_Baum@rush.edu.
authors: Linda L
authors: LL
authors: Baum
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects*; D002452:Cell Count; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013154:Spleen / Q000276:immunology; D019966:Substance-Related Disorders / Q000097:blood / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; D008694:Methamphetamine
keywords: CD4 T cells; Inflammatory cytokines; Methamphetamine; Rat; Self-administration