Allergic asthma is thought to be regulated by Th2 cells, and inhibiting this response is a promising mode of intervention. Many studies have focused on differentiation of Th cells to the Th1 or Th2 subset in vitro. IL-4 is essential for Th2 development, while IL-12 induces Th1 development, which can be enhanced by IL-18. In the present study, we investigated whether IL-12 and IL-18 were able to interfere in Th2 development and the associated airway symptoms in a mouse model of allergic asthma. Mice were sensitized with OVA using a protocol that induces IgE production. Repeated challenges by OVA inhalation induced elevated serum levels of IgE, airway hyperresponsiveness, and a predominantly eosinophilic infiltrate in the bronchoalveolar lavage concomitant with the appearance of Ag-specific Th2-like cells in lung tissue and lung-draining lymph nodes. Whereas treatments with neither IL-12 nor IL-18 during the challenge period were effective, combined treatment of IL-12 and IL-18 inhibited Ag-specific Th2-like cell development. This inhibition was associated with an absence of IgE up-regulation, airway hyperresponsiveness, and cellular infiltration in the lavage. These data show that, in vivo, the synergistic action of IL-12 and IL-18 is necessary to prevent Th2-like cell differentiation, and consequently inhibits the development of airway symptoms in a mouse model of allergic asthma.

JOURNAL ARTICLE Animal Asthma/IMMUNOLOGY/*THERAPY Biological Response Modifiers/PHARMACOLOGY/*THERAPEUTIC USE Bronchial Hyperreactivity/CHEMICALLY INDUCED/IMMUNOLOGY/PATHOLOGY/ *PREVENTION & CONTROL Bronchoalveolar Lavage Fluid/CYTOLOGY Cell Differentiation/DRUG EFFECTS Cells, Cultured Cytokines/SECRETION Drug Synergism Eosinophilia/CHEMICALLY INDUCED/IMMUNOLOGY/*PREVENTION & CONTROL IgE/*BLOOD Interleukin-12/PHARMACOLOGY/*THERAPEUTIC USE Interleukin-18/PHARMACOLOGY/*THERAPEUTIC USE Lung/PATHOLOGY/SECRETION Lymph Nodes/PATHOLOGY/SECRETION Male Mice Mice, Inbred BALB C Ovalbumin/IMMUNOLOGY/TOXICITY Recombinant Proteins/PHARMACOLOGY/THERAPEUTIC USE Specific Pathogen-Free Organisms Support, Non-U.S. Gov't Th2 Cells/*DRUG EFFECTS/IMMUNOLOGY

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