Methamphetamine (MA) use and MA-induced psychosis are associated with increasing aberrations in the compensatory immunoregulatory system, interleukin-1α, and CCL5 levels

Abstract

Abstract Comprehensive immunological profiles have not been studied in relation to methamphetamine (MA) use, MA dependency, or MA-induced psychosis (MAP). Using the BioPlex Pro Human Cytokine 48-Plex panel, this study measured M1 macrophage, T helper (Th)-1, Th-2, growth factor, and chemokine profiles, as well as the immune inflammatory response system (IRS) and compensatory immunoregulatory system (CIRS) in peripheral blood samples from patients with MA use (n=51), MA dependence (n=47), and MAP (n=43) in comparison with healthy controls (n=43). We discovered that persistent MA use had a robust dose-dependent suppressive impact on all immunological profiles, suggesting extensive immunosuppression. The most reliable biomarker profile of MA use is the combination of substantial CIRS suppression and a rise in selected pro-inflammatory cytokines, namely CCL27 (CTACK), CCL11 (eotaxin), and interleukin (IL)-1α. In addition, MA dependency is related with a more severe immunosuppression, as demonstrated by lower stem cell factor and higher IL-10 levels. MAP is related with a significant decrease in all immunological profiles, particularly CIRS, and an increase in CCL5 (RANTES), IL-1α, and IL-12p70 signaling. In conclusion, long-term MA use and dependency severely undermine immune homeostasis. This results in widespread immunosuppression, which may increase the likelihood of infectious and immune illness or exacerbate disorders such as hepatitis and AIDS. Elevated levels of CCL5, CCL11, CCL27, IL-1α, and/or IL-12p70 may be associated with severe peripheral (atherosclerosis, cutaneous inflammation, immune aberrations, hypospermatogenesis) and central (neuroinflammation, neurotoxic, neurodegenerative, depression, anxiety and psychosis) side effects.