Lidocaine inhibits secretion of IL-8 and IL-1β and stimulates secretion of IL-1 receptor antagonist by epithelial cells

M. Lahav, M. Levite, L. Bassani, A. Lang, H. Fidder, R. Tal, S. Bar-Meir, L. Mayer, Y. Chowers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Lidocaine and related local anaesthetics have been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms underlying their therapeutic effect are poorly defined. Intestinal epithelial cells play an important role in the mucosal inflammatory response that leads to tissue damage in UC via the secretion of pro-inflammatory cytokines and chemokines. The aim of this study was to evaluate the direct immunoregulatory effect of lidocaine on pro-inflammatory cytokine and chemokine secretion from intestinal epithelial cells. HT-29 and Caco-2 cell lines were used as a model system and treated with lidocaine and related drugs. The expression of IL-8, IL-1β and the IL-1 receptor antagonist (RA) were assessed by ELISA and quantification of mRNA. In further experiments, the effect of lidocaine on the secretion of IL-8 from freshly isolated epithelial cells stimulated with TNFα was tested. Lidocaine, in therapeutic concentrations, inhibited the spontaneous and TNFα-stimulated secretion of IL-8 and IL-1β from HT-29 and Caco-2 cell lines in a dose-dependent manner. Similarly, suppression of IL-8 secretion was noted in the freshly isolated epithelial cells. Other local anaesthetics, bupivacaine and amethocaine, had comparable effects. Lidocaine stimulated the secretion of the anti-inflammatory molecule IL-1 RA. Both the inhibitory and the stimulatory effects of lidocaine involved regulation of transcription. The results imply that the therapeutic effect of lidocaine may be mediated, at least in part, by its direct effects on epithelial cells to inhibit the secretion of pro-inflammatory molecules on one hand while triggering the secretion of anti-inflammatory mediators on the other.

Original languageEnglish
Pages (from-to)226-233
Number of pages8
JournalClinical and Experimental Immunology
Volume127
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Chemokines
  • Cytokines
  • IL-1 receptor antagonist
  • Intestinal epithelial cells
  • Local anaesthetics

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