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 comorbidity 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 self-administration session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γand TNF-α, and frequencies of CD4+, CD8+, CD200+ and CD11b/c+ lymphocytes in the spleen. Rats that self-administer 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. Or 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 African American men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection.

Methamphetamine and its immune-modulating effects

“…Furthermore, a better understanding of the link between METH use in the younger years, and its consequence to health outcomes in the long term (after METH has been stopped) in regards to increased risk of communicable and non-communicable diseases and accelarating the ageing process are required. Macrophages ↑↑ IL-8, IL-1 and TNF- in LPS-treated macrophages [25] ↑↑ Activated brain macrophages [36] T cells ↓ CD4 ↑ CD8 Effect of METH on systemic immune system [126] ↓ CD4…”

Role of Autophagy in HIV Pathogenesis and Drug Abuse

“…Studies have found that morphine suppressed T cell activation in the lymph node, paralleled with a decrease in activation levels of T cells in peripheral blood in nonhuman primates [126]. Methamphetamine has been shown to accelerate the premature demise of activated T cells [127], and reduce the number of dendritic cells and natural killer cells [128,129]. Other than that, excessive reactive oxygen species is produced when astrocytic cells are treated with methamphetamine via CYP2E1, leading to apoptotic cell death [95].…”

Methamphetamine Enhances HIV-1 Replication in CD4+ T-Cells via a Novel IL-1β Auto-Regulatory Loop

“…The drug can enhance virus replication and clinical progression, often promoting poor adherence to anti-retroviral therapies. Meth has also been shown to modulate inflammatory cytokine expression (10)(11)(12). Specifically, Meth has been reported to enhance IL-1β expression in dendritic cells and the rat hypothalamus (13,14).…”

“…Distinct from HIV-1 infection, Meth has also been shown to alter the expression of inflammatory cytokines in several murine tissues, in the serum of self-administering rats, and in the plasma of human subjects in early recovery from addiction (10)(11)(12). Specifically, Meth increased Interleukin-1β (IL-1β) mRNA and protein expression in dendritic cells, and in the rat hypothalamus (13,14).…”