H. Renz et al., PREVENTION OF THE DEVELOPMENT OF IMMEDIATE HYPERSENSITIVITY AND AIRWAY HYPERRESPONSIVENESS FOLLOWING IN-VIVO TREATMENT WITH SOLUBLE IL-4 RECEPTOR, International archives of allergy and immunology, 109(2), 1996, pp. 167-176
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.