4.7 Article

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

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TRANSLATIONAL PSYCHIATRY
Volume 13, Issue 1, Pages -

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SPRINGERNATURE
DOI: 10.1038/s41398-023-02645-6

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There are only a few studies on the immunological profiles of methamphetamine use, dependence, and induced psychosis. This study found that long-term methamphetamine use has a strong immunosuppressive impact on all immunological profiles. Methamphetamine use is associated with a combination of suppressed immune response and increased pro-inflammatory cytokines. Methamphetamine dependence is linked to increased immunosuppression and decreased stem cell factor levels. Methamphetamine-induced psychosis is related to significant decreases in all immunological profiles and increased pro-inflammatory cytokine signaling. The widespread immunosuppression caused by methamphetamine use may increase the risk of infectious and immune-related diseases.
There are only a few studies reporting on the immunological profiles of methamphetamine (MA) use, MA dependency, or MA-induced psychosis (MAP). 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 controls (n = 32). We discovered that persistent MA use had a robust immunosuppressive impact on all immunological profiles. 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)-1 alpha. In addition, MA dependency is associated with increased immunosuppression, as demonstrated by lower stem cell factor levels and higher IL-10 levels. MAP is related to a significant decrease in all immunological profiles, particularly CIRS, and an increase in CCL5 (RANTES), IL-1 alpha, and IL-12p70 signaling. In conclusion, long-term MA use and dependency severely undermine immune homeostasis, whereas MAP may be the consequence of increased IL-1 alpha - CCL5 signaling superimposed on strongly depleted CIRS and Th-1 functions. The widespread immunosuppression established in longstanding MA use may increase the likelihood of infectious and immune illness or exacerbate disorders such as hepatitis and AIDS. Furthermore, elevated levels of CCL5, CCL11, CCL27, IL-1 alpha, and/or IL-12p70 may play a role in the peripheral (atherosclerosis, cutaneous inflammation, immune aberrations, hypospermatogenesis) and central (neuroinflammation, neurotoxic, neurodegenerative, depression, anxiety, and psychosis) side effects of MA use.

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