PREVENTION OF THE DEVELOPMENT OF IMMEDIATE HYPERSENSITIVITY AND AIRWAY HYPERRESPONSIVENESS FOLLOWING IN-VIVO TREATMENT WITH SOLUBLE IL-4 RECEPTOR

The effects of local versus systemic treatment with soluble IL-4 recep tors (sIL-4R) were tested in a model of allergen-induced immediate hyp ersensitivity responses in BALB/c mice. Mice sensitized through the ai rways to ovalbumin (OVA) by ultrasonic nebulization once a week for 4 weeks developed increased serum anti-OVA IgE and IgG1 antibody titers and these were accompanied by immediate-type skin test responses to th e allergen. These responses were also associated with the development of increased airway responsiveness (AR) as monitored by electrical fie ld stimulation of tracheal smooth muscle preparations in vitro. Sensit ized mice, treated by intraperitoneal injections of sIL-4R (150 mu g/i njection) administered in parallel to the sensitization protocol, deve loped significant suppression of anti-OVA IgE, anti-OVA IgG1 antibody production and of immediate cutaneous hypersensitivity responses. Airw ay responsiveness was normalized to some extent. Total IgE production was only slightly reduced. These effects were comparable to the findin gs following intraperitoneal injection of monoclonal anti-IL-LF antibo dy. Administration of sIL-4R via the airways was also effective in inh ibiting the development of immediate hypersensitivity responses, inclu ding IgE production, and was more potent in normalizing airway respons iveness. These effects were achieved at lower concentrations than need ed for systemic treatment. These data suggest that delivery of sIL-4R via the airways can effectively modulate the development of immediate hypersensitivity and airway hyperresponsiveness in response to aerosol ized allergen.