TY - JOUR
T1 - Lidocaine down-regulates nuclear factor-κB signalling and inhibits cytokine production and T cell proliferation
AU - Lahat, A.
AU - Horin, S. B.
AU - Lang, A.
AU - Fudim, E.
AU - Picard, O.
AU - Chowers, Y.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - Cytokine
KW - Inflammation
KW - Lidocaine
KW - NF-κB
KW - T cell
UR - http://www.scopus.com/inward/record.url?scp=42049086558&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2249.2008.03636.x
DO - 10.1111/j.1365-2249.2008.03636.x
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C2 - 18355353
AN - SCOPUS:42049086558
SN - 0009-9104
VL - 152
SP - 320
EP - 327
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 2
ER -