LOCAL TREATMENT WITH IL-12 IS AN EFFECTIVE INHIBITOR OF AIRWAY HYPERRESPONSIVENESS AND LUNG EOSINOPHILIA AFTER AIRWAY CHALLENGE IN SENSITIZED MICE

Background: Systemic administration of IL-12 can prevent airway hyperr esponsiveness (AHR) in mice after sensitization and repeated allergen challenge. However, systemic IL-12 has been associated with severe adv erse effects. Objective: We determined whether IL-12 administration to the airways in a dose sufficiently low so as not to result in systemi c effects can modify allergic inflammation and AHR after allergen chal lenge. Methods: Mice were sensitized to ovalbumin by intraperitoneal i njection and challenged with ovalbumin aerosol on 3 consecutive days. During the period of challenge, IL-12 was administered intranasally fo llowing 2 regimens, designated high (500 ng) or low (50 ng). We monito red airway responsiveness to inhaled methacholine by barometric body p lethysmography, lung inflammatory cells, local cytokine production, an d, to assess systemic effects of IL-12 treatment, spleen weights and n umbers of eosinophils in the bone marrow. Results: Allergen challenge resulted in increases in airway responsiveness and in numbers of lung eosinophils. These increases were prevented by both high- and ion-dose IL-12, Additionally, IL-12 administration resulted in enhanced local interferon-gamma production and prevented the increases in Local IL-4 and IL-5 production after airway challenge. A high dose, but not a low dose, of IL-12 resulted in increased spleen weights and prevented the increase in numbers of bone marrow eosinophils after allergen challen ge. Conclusion: These data indicate that local administration of IL-12 can prevent AHR and reduce lung eosinophilia after allergen challenge in sensitized mice without eliciting systemic adverse effects. IL-12 exerts these effects by inducing local T-H1-type responses in the airw ays in a setting that is normally dominated by T-H2-type responses.