Background: Methamphetamine and related drugs are highly abused with potent stimulatory effects in the central nervous system. Chronic abuse of these drugs leads to significant cardio- and neurotoxicity. In animal models, these effects are mediated, in part, by inflammation. However, to date, clinical evidence for methamphetamine-induced peripheral and neuroinflammation is lacking. The aim of the work was to determine whether methamphetamine use is associated with changes in peripheral levels of pro-inflammatory cytokines, namely TNF-α, IL-1β, and IL-6.

Subjects and methods: Peripheral cytokine levels were assessed in methamphetamine users (n=94) and in two groups of control subjects: non-drug users (n=58) and cannabis users (n=53). To determine whether these changes were due to direct activation of immune cells, peripheral blood mononuclear cells (PBMCs) were isolated from healthy, non-drug users and were stimulated with methamphetamine.

Results and discussion: Significant increases were detected in the levels of two pro-inflammatory cytokines in methamphetamine users relative to healthy controls. In PBMCs levels of three pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were decreased upon exposure to methamphetamine, while the levels of IL-10, an anti-inflammatory cytokine, were increased, suggesting that the drug has immunosuppressant properties. This paradoxical result suggests that an increase in the levels of pro-inflammatory cytokines in methamphetamine users is not due to direct activation of immune cells, rather it may represent an inflammatory response elsewhere in the body, possibly as a result of cardio- or neurotoxicity. Alternatively, acute methamphetamine administration may suppress cytokine release. With chronic exposure, however, an upregulation occurs so that basal cytokine levels are elevated in chronic users not under the influence of the drug.