IFN-γ-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma

James S. Wild, Anastasia Sigounas, Nilanjana Sur, Mohammed S. Siddiqui, Rafeul Alam, Masashi Kurimoto, Sanjiv Sur

Research output: Contribution to journalArticle

217 Scopus citations

Abstract

We investigated the effects of IFN-γ-inducing factor (IL-18) in a ragweed (RW) mouse model of allergic asthma. Administration of IL-18 in conjunction with allergic sensitization and challenge in wild-type, but not IFN-γ(-/-) mice, inhibited the bronchoalveolar lavage (BAL) eosinophilia induced by RW challenge, and increased serum levels of RW-specific IgG2a and production of IFN-γ from splenocytes cultured with RW, indicating a critical role for IFN-γ in mediating these effects. Paradoxically, the same treatment schedule in WT mice increased serum levels of RW-specific IgE and IgG1, and production of IL-4 and IL-5 from splenocytes cultured with RW. When the effects of the same IL-18 treatment schedule were allowed to mature for 3 wk, the inhibition of lung eosinophil recruitment was replaced by augmentation of lung eosinophil recruitment. In another experiment, IL-18 administered only with allergic sensitization increased BAL eosinophilia and lung expression of IL-5 and IFN-γ, while IL-18 administered only with RW challenge decreased BAL eosinophilia and increased lung IFN-γ expression, while lung expression of IL-5 remained unchanged. IL-18 administered without RW or adjuvant to naive mice increased total serum IgE levels. Finally, intrapulmonary administrations of IL-18 plus RW in naive mice dramatically increased Th2 cytokine production, IgE levels, eosinophil recruitment, and airway mucus, demonstrating induction of allergic sensitization. This is the first report demonstrating that IL-18 promotes a Th2 phenotype in vivo, and potently induces allergic sensitization. These results suggest that IL-18 may contribute to the pathogenesis of allergic asthma.

Original languageEnglish (US)
Pages (from-to)2701-2710
Number of pages10
JournalJournal of Immunology
Volume164
Issue number5
DOIs
StatePublished - Mar 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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