Resistance to antigen-induced airway hyperresponsiveness requires endogenous production of IL-12

Andrea Keane-Myers, Maria Wysocka, Giorgio Trinchieri, Marsha Wills-Karp

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63 Scopus citations


We have demonstrated previously that susceptibility of murine strains to the development of allergic airway responses is associated with a type 2 cytokine pattern. In the present study, we examine the in vivo role of IL-12 in the immune response to allergen exposure in susceptible (A/J) and resistant (C3H/HeJ, C3H) strains of mice. OVA sensitization and challenge induced significant increases in airway reactivity in A/J mice as compared with their PBS-challenged controls, while no increases in airway reactivity were observed in OVA-challenged C3H mice. OVA exposure of A/J mice resulted in marked increases in the Th2 cytokines, IL-4 and IL-10, in the bronchoalveolar lavage fluid, whereas increases in IFN-γ were observed in C3H mice. Strikingly, anti-IL-12 mAb (1 mg/mouse) treatment resulted in threefold increases in airway reactivity in OVA-challenged resistant C3H mice, concomitant with significant increases in bronchoalveolar lavage levels of Th2 cytokines and decreases in IFN-γ. IL-12 depletion of C3H mice also suppressed OVA-specific serum IgG2a levels and increased both serum OVA- specific IgG1 and IgE levels. Blockade of endogenous IL-12 levels in susceptible A/J mice resulted in further augmentation of type 2 immune responses. These results demonstrate that endogenous production of IL-12 is essential for resistance to Ag-induced airway hyperresponsiveness, and furthermore, that dysregulation of IL-12 production may lead to the development of deleterious type 2 immune responses to inhaled allergens.

Original languageEnglish (US)
Pages (from-to)919-926
Number of pages8
JournalJournal of Immunology
Issue number2
StatePublished - Jul 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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