Cocaine Use Disorder Is Associated With Changes in Th1/Th2/Th17 Cytokines and Lymphocytes Subsets

Abstract

Background: Cocaine is a psychostimulant drug with high addictive proprieties. Evidence suggests that cocaine use leads to critical changes in the immune system, with significant effects on T, B, and natural killer (NK) cells and influencing peripheral levels of cytokines. The presence of abstinence-related symptoms during detoxification treatment is known to influence the prognosis. Here, our aim was to investigate immune profiles in women with cocaine use disorder (CUD) according to withdrawal symptoms severity.Methods: Blood samples and clinical data were collected at onset of detoxification treatment of 50 women with CUD. The patients were stratified according to Cocaine Selective Severity Assessment (CSSA) scores in low withdrawal (L-W) and high withdrawal (H-W) categories. In addition, we also included a control group with 19 healthy women as reference to immune parameters. Peripheral blood was collected and lymphocyte subsets were phenotyped by multi-color flow cytometry (B cells, CD4+ T, CD8+ T, NK cells, and different stages of T-cell differentiation). PBMCs from patients and healthy controls were stimulated in vitro with phytohemagglutinin (1%) for 72 h to assess the production of Th1/Th2/Th17 cytokines.Results: Following stimulation, lymphocytes from women with CUD produced increased levels of Th1/Th2/Th17 cytokines. However, higher levels of IL-2 and IL-17 were observed only in the L-W group, while higher levels of IL-6 were detected in the H-W group compared to controls. H-W group showed lower percentage of early-differentiated Th cells (CD4+CD27+CD28+), elevated percentage of Th cells (CD3+CD4+), intermediate-differentiated Th cells (CD4+CD27−CD28+), and B cells (CD3−CD19+). Both CUD groups showed decreased percentages of naïve T cells (CD3+CD4+CD45RA+ and CD3+CD8+CD45RA+).Conclusion: Our data demonstrated that CUD can lead to increased production of Th1/Th2/Th17 cytokines and lymphocyte changes.

Intravenous haloperidol and cocaine alter the distribution of T CD4+ and B lymphocytes and NKT cells in rats

“…Serum concentrations of IL-4 and IFN-γ both decreased after cocaine and haloperidol treatment; however, due to considerable inter-individual variability, we did not find the effects to be statistically significant. Results suggest that, for some individuals, haloperidol and cocaine may suppress IL-4 and IFN-γ signaling [18,55]. Moreover, the concentrations of IL-4 and IFN-γ that we detected in our study were comparable to that of control groups in other reports [56,57], suggesting that manipulations of chronically implanted catheters per se did not induce pronounced inflammation.…”

“…Cocaine suppresses the immune system via both central and peripheral mechanisms [15][16][17][18]. The hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system are the primary pathways through which cocaine modulates the immune system [17,19,20].…”

Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities

“…Importantly, no effective medications exist that successfully treat cocaine use disorders (CUDs). Studies in humans have demonstrated that CUDs are associated with altered serum levels of pro-and antiinflammatory cytokines (Moreira et al, 2016;Zaparte et al, 2019). As well, serum cytokine levels may be useful indicators for assessing the severity for CUDs and identifying effective treatment strategies, although sex differences and psychiatric comorbidity are important factors to consider (Araos et al, 2015;Pedraz et al, 2015;Maza-Quiroga et al, 2017;Pianca et al, 2017).…”

Clinical vulnerability for severity and mortality by COVID-19 among users of alcohol and other substances

“…In addition, immunological alterations have been observed in individuals with SUD ( Cohen et al, 1993 ; Schuch-Goi et al, 2017 ; Sureshchandra et al, 2019 ; Zaparte et al, 2019 ). Studies showed that alcohol and cocaine/crack abuse increase the risk for infectious diseases ( Butler et al, 2017 ; Collaborators, 2018 ; Halpern et al, 2017 ; Peacock et al, 2018 ; WHO, 2018 ).…”