Sulfonylureas inhibit cytokine-induced eosinophil survival and activation

Jennifer L. Bankers-Fulbright, Gail M. Kephart, David A. Loegering, Annabel L. Bradford, Shinji Okada, Hirohito Kita, Gerald J. Gleich

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Eosinophils play a key role in the pathogenesis of asthma and other allergic inflammatory diseases. We have previously shown that treatment of eosinophils with lidocaine preferentially inhibits IL-5-induced survival. This inhibition cannot be overcome by increasing concentrations of IL-5 and is not due to the blocking of Na+ channels by lidocaine. Here we report that one class of K+ channel blockers, the sulfonylureas, inhibits eosinophil survival in a manner similar to lidocaine. The sulfonylurea glyburide inhibits eosinophil survival even at high concentrations of IL-5. In contrast, increasing concentrations of IL-3 or granulocyte-macrophage CSF overcome glyburide inhibition. Glyburide also blocks cytokine-induced eosinophil superoxide production. Similar results were seen with the sulfonylureas tolbutamide and glipizide. Interestingly, the effects of glyburide are not antagonized by the ATP-sensitive K+ channel openers cromakalim, pinacidil, or diazoxide. Although Scatchard analysis of [3H]glyburide binding to eosinophil membranes indicated that the high affinity sulfonylurea receptor (SUR1) is not present on eosinophils, human eosinophils do express mRNA homologous to the sulfonylurea receptor family, in keeping with the presence of a sulfonylurea receptor. Finally, coculture of eosinophils with combinations of glyburide, lidocaine, and dexamethasone resulted in synergistic inhibition of cytokine-mediated eosinophil survival and superoxide production. These results have intriguing clinical implications for the treatment of eosinophil-associated diseases.

Original languageEnglish (US)
Pages (from-to)5546-5553
Number of pages8
JournalJournal of Immunology
Volume160
Issue number11
StatePublished - Jun 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Bankers-Fulbright, J. L., Kephart, G. M., Loegering, D. A., Bradford, A. L., Okada, S., Kita, H., & Gleich, G. J. (1998). Sulfonylureas inhibit cytokine-induced eosinophil survival and activation. Journal of Immunology, 160(11), 5546-5553.