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

Clin Exp Immunol. 2008 May;152(2):320-7. doi: 10.1111/j.1365-2249.2008.03636.x. Epub 2008 Mar 18.


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.

MeSH terms

  • Anesthetics, Local / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytokines / biosynthesis*
  • Dose-Response Relationship, Immunologic
  • Down-Regulation / drug effects
  • Humans
  • Immune Tolerance / drug effects
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics
  • Jurkat Cells
  • Lidocaine / pharmacology*
  • Lymphocyte Activation / drug effects
  • NF-kappa B / metabolism*
  • RNA, Messenger / genetics
  • Signal Transduction / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics


  • Anesthetics, Local
  • Cytokines
  • Interleukin-2
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Lidocaine