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

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. Our message: ″cease using MA, or better yet, never begin using MA″.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by the Centre for Addiction Studies, Department of Psychiatry, Faculty of Medicine, Chulalongkorn University and the Thai Health Promotion Foundation.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee / Institutional Review Board of the Faculty of Medicine of Chulalongkorn University and the Princess Mother National Institute on Drug Abuse and Treatment gave ethical approval for this work (No. 28/2565).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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