Lidocaine down-regulates nuclear factor-κB signalling and inhibits cytokine production and T cell proliferation

A. Lahat, S. B. Horin, A. Lang, E. Fudim, O. Picard, Y. Chowers

Research output: Contribution to journalArticlepeer-review

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)-α 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-α secretion by Jurkat T cells at the protein and mRNA levels. Moreover, lidocaine reduced nuclear factor-κB (NF-κB) signalling in clinically relevant concentrations. Similarly, proliferation of anti-CD3 stimulated PB T cells was abrogated significantly by lidocaine, and the percentage of interferon-γ- and TNF-α-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-κB signalling.

Original languageEnglish
Pages (from-to)320-327
Number of pages8
JournalClinical and Experimental Immunology
Volume152
Issue number2
DOIs
StatePublished - May 2008

Keywords

  • Cytokine
  • Inflammation
  • Lidocaine
  • NF-κB
  • T cell

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