title: Th17/Treg imbalance in opioids and cannabinoids addiction: relationship to NF-κB activation in CD4+ T cells.
abstract: Opioids are widely used for the treatment of severe pain. However, opioids, particularly morphine, is known to cause immunosuppression. This study investigated the impact of morphine and cannabinoids addiction on CD4+ T cell mediated immunity. We hypothesize that, accompanied immunosuppression is attributed to reduced T cell activation with an extent of affection to the cytoplasmic activity of the biologically active transcription factor nuclear factor-κB (NF-κB) which play crucial role in T-cell activation. A disturbance in cytokine balance, in particular, interleukin-17 (IL-17)/interleukin-10 (IL-10) production may also act as a mechanism of immunosuppression. Peripheral blood CD4+ T cells from 45 chronic morphine and cannabinoid addicts and 10 controls with no current or past history of drug abuse; were stimulated by anti-CD3 antibody plus phytoheamagglutinin (PHA). Activation of the NF-κB signaling pathway was examined by analyzing NF-κBp65 in a solid phase sandwich ELISA. IL-17/IL-10 balance was assessed using quantitative ELISA on cultured CD4+ T cells supernatants. We found that, morphine and cannabinoids inhibited NF-κB signaling in activated T cells of addicts, whereas it enhanced activated T cell apoptosis as measured by quantitative in vitro determination of cytoplasmic histone-associated DNA fragmentation following induced cell death. These effects of morphine and cannabinoids T cell suppression were accompanied by elevation of IL-10 level and concomitant reduction in IL-17 secretion from cultured CD4+ T cells. We concluded that Th17/Treg imbalance may be attributed to inhibited NF-κB activity in CD4+ T cells under the effect of morphine and cannabinoids addiction.
authors: S
authors: S
authors: Abo-Elnazar
authors: M
authors: M
authors: Moaaz
authors: H
authors: H
authors: Ghoneim
authors: T
authors: T
authors: Molokhia
authors: W
authors: W
authors: El-Korany
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D008297:Male; D002189:Marijuana Abuse / Q000276:immunology* / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology*; D009293:Opioid-Related Disorders / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C508609:IL10 protein, human; D020381:Interleukin-17; D016328:NF-kappa B; D016753:Interleukin-10