Influence of Endogenous Opioid Systems on T Lymphocytes as Assessed by the Knockout of Mu, Delta and Kappa Opioid Receptors

Abstract

Here, we evaluated the influence of endogenous opioid activation on immune responses by examining consequences of all three opioid receptor gene (mu, delta and kappa) inactivation. In triple-opioid receptor knockout mice, splenocytes and thymocytes numbers, lymphocyte subsets as well as proliferation and cytokines induced by in vitro stimulation of T lymphocytes were measured. Compared with wild-type mice, similar lymphocyte distribution in thymus and spleen as well as comparable T lymphocyte proliferation were observed, while lower levels of IL-2 and IFNγ as well as higher levels of IL-4 and IL-10 were found in triple-opioid receptor knockout mice. Together, our results indicate a shift from TH1 to TH2 cytokines in triple-opioid receptor knockout animals, suggesting that global endogenous opioid tone drives T lymphocytes toward a TH1 profile under non-pathological conditions.

Whole-Genome Cardiac DNA Methylation Fingerprint and Gene Expression Analysis Provide New Insights in the Pathogenesis of Chronic Chagas Disease Cardiomyopathy

“…In addition, PENK drives T cells toward a Th1 profile and activates macrophages [ 35 , 36 ]. Finally, RUNX3 , upregulated in CCC, belongs to the Runt family of transcription factors.…”

INFLUENCE OF POLYOXIDONIUM, Poly(I:C), DALARGIN ON THE PROTECTIVE EFFICACY OF YERSINIA PESTIS VACCINE STRAIN EV LINE NIIEG IN EXPERIMENTAL PLAGUE

“…Синтетический аналог лей-энкефалинадаларгин -взаимодействует преимущественно с δ-опиоидными рецепторами, экспрессия которых выявлена на мононуклеарных клетках различных лимфоидных органов, Т-клетках периферической крови человека [30,31]. Агонисты δ-опиоидных рецепторов модулируют пролиферацию Т-клеток, продукцию IL-2, хемотаксис, активность циклазных систем, проводимость мембран для ионов калия и кальция [19,21]. Даларгин стимулирует in vitro продукцию IL-17, IFNγ, IL-4 клетками крови вакцинированных ВЧЖ лиц, у ревакцинированных -только IL-17 и IFNγ [11].…”

Drugs of Abuse Effects on Immunity and Microbial Pathogenesis

“…While the previous articles focus on the effects of exogenous application of abused substances, the original article by Karaji et al (2011) and the brief report by Kaminsky and Rogers (2011) addresses the influence of endogenous peptides on immune responses (Kaminsky and Rogers 2011;Karaji et al 2011). Unexpectedly, a shift from TH1 to TH2 cytokines is observed in triple-opioid receptor knockout animals, implicating endogenous opioids in polarizing T lymphocytes toward a TH1 profile under non-pathological conditions (Karaji et al 2011). Kaminsky and Rogers (2011) on the other hand offer a different perspective investigating the role of crossdesensitization between G protein-coupled receptors (GPCRs) in the regulation of the immune response (Kaminsky and Rogers 2011).…”