title: Fentanyl Suppresses the Survival of CD4+T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKKs-mediated NF-κB Activation.
abstract: The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anaesthetic on T lymphocytes isolated from human umbilical cord blood in vitro. The percentages of CD4+, CD8+and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitro were analysed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4 and IL-17 secreted by activated CD4+T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signalling pathway proteins were determined by Western blotting. Effects of fentanyl on IKK and p65 expression promoter activities were analysed by luciferase assay. Fentanyl decreased the percentages and amounts of CD4+, CD8+and Foxp3+Treg T lymphocyte subsets in UBMCs in a dose-dependent manner. Fentanyl inhibited the proliferation and induced apoptosis of activated CD4+T cells dose dependently. Fentanyl could not reverse the increase of cell proliferation in activated groups to be equivalent with those in inactivated group. Secretions of IFN-γ, IL-2 and IL-4 cytokines were significantly decreased by moderate to high dose of fentanyl compared with controls. No significant differences were observed in protein expressions of MAPK pathway. In addition, fentanyl suppressed the IKKs-mediated activation of NF-κB. This study demonstrates that fentanyl exerts immunosuppressive effects on T lymphocytes obtained from UBMCs. Thus, the clinical application of fentanyl would not only relieve pain caused by surgery but regulate immune responses post-operation possibly through inhibition of IKKs-mediated NF-κB activation.
authors.affiliation: Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, China.
authors.forename: K
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang, China.
authors.forename: P
authors.initials: P
authors.lastname: Ma
authors.affiliation: ICU, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, China.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: The Fourth Hospital of Shijiazhuang, Shijiazhuang, China.
authors.forename: Q
authors.identifier: http://orcid.org/0000-0002-6144-492X
authors.initials: Q
authors.lastname: Cao
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005283:Fentanyl / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000759:Adjuvants, Anesthesia; D016207:Cytokines; D016328:NF-kappa B; D008156:Luciferases; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases; D005283:Fentanyl