Dexamethasone or cyclosporin a suppress mast cell-leukocyte cytokine cascades: Multiple mechanisms of inhibition of IgE- and mast cell-dependent cutaneous inflammation in the mouse

Barry K. Wershil*, Glenn T. Furuta, Jackie A. Lavigne, Anjona Roy Choudhury, Zhen S. Wang, Stephen J. Galli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

In allergic diseases, exposure of sensitized subjects to allergen induces the activation of tissue mast cells that results in an immediate-type hypersensitivity response and, in some individuals, a late phase response. We previously have reported that the neutrophil infiltration associated with IgE-dependent cutaneous inflammation in mice is mast cell-dependent and that TNF-α contributes significantly to this response. We report here that either dexamethasone or cyclosporin A can inhibit mouse mast cell TNF-α production in vitro, and that these agents also can significantly suppress the tissue swelling and leukocyte infiltration associated with two forms of TNF-α- associated inflammation in vivo: the entirely IgE- and mast cell-dependent inflammation at sites of passive cutaneous ana phylaxis reactions and the entirely TNF-α-dependent inflammation that is elicited by the direct intradermal injection of recombinant mouse TNF-α. Taken together, our in vitro and in vivo findings in mice indicate that dexamethasone or cyclosporin A can have at least three actions that interfere with the pathogenesis of IgE, mast cell-, and cytokine-dependent inflammatory reactions: suppression of the IgE-dependent increase in TNF-α mRNA by mast cells, inhibition of the IgE-dependent production of TNF-α protein by mast cells, and diminution of the responsiveness of target cells to TNF-α. Our findings in mice raise the possibility that similar actions of these agents in humans may account for some of the clinical efficacy of corticosteroids and cyclosporin A in allergic diseases.

Original languageEnglish (US)
Pages (from-to)1391-1398
Number of pages8
JournalJournal of Immunology
Volume154
Issue number3
StatePublished - 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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