title: Lidocaine down-regulates nuclear factor-kappaB signalling and inhibits cytokine production and T cell proliferation.
abstract: Lidocaine is a commonly used local anaesthetic agent which has also been found to possess anti-inflammatory activity in several disorders. However, the mechanism of this effect has been little explored. The aim of this study was to investigate the effect of lidocaine on stimulated human T cells. The effect of lidocaine on Jurkat T cells was examined by enzyme-linked immunosorbent assay (ELISA) to determine secretion of interleukin (IL)-2, and by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] viability assay. Tumour necrosis factor (TNF)-alpha and IL-2 mRNA expression was determined by reverse transcription-polymerase chain reaction. In addition, the effect of lidocaine on the proliferation of freshly isolated peripheral blood (PB) CD3(+) T cells was examined by carboxyfluorescein succinimidyl ester dilution. Apoptosis induction and cytokine production and secretion were determined by annexin V/PI assay, intracellular immunostaining and ELISA respectively. The results showed that lidocaine exerts a dose-dependent inhibition of IL-2 and TNF-alpha secretion by Jurkat T cells at the protein and mRNA levels. Moreover, lidocaine reduced nuclear factor-kappaB (NF-kappaB) signalling in clinically relevant concentrations. Similarly, proliferation of anti-CD3 stimulated PB T cells was abrogated significantly by lidocaine, and the percentage of interferon-gamma- and TNF-alpha-producing T cells was diminished after culture with this agent. In both experimental systems, lidocaine's effect was not mediated by cytotoxic mechanism, as no significant apoptosis or necrosis was demonstrated following co-culture of T cells with this drug. In conclusion, lidocaine's anti-inflammatory effect may be mediated by a drug-induced abrogation of T cell proliferation and cytokine secretion independent of cell death. These effects are mediated at least partly by inhibition of NF-kappaB signalling.
authors: Department of Gastroenterology, Chaim Sheba Medical Center affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. zokadi@gmail.com
authors: A
authors: A
authors: Lahat
authors: S
authors: S
authors: Ben-Horin
authors: S B
authors: SB
authors: Horin
authors: A
authors: A
authors: Lang
authors: E
authors: E
authors: Fudim
authors: O
authors: O
authors: Picard
authors: Y
authors: Y
authors: Chowers
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D019169:Jurkat Cells; D008012:Lidocaine / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000779:Anesthetics, Local; D016207:Cytokines; D007376:Interleukin-2; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008012:Lidocaine