IL-4 Receptor Antagonist Effective in Mouse Asthma Model
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WESTPORT, CT (Reuters Health) May 09 - A mutant IL-4 protein that blocks the IL-4 receptor prevented antigen-induced airway eosinophilia and airway hyperresponsiveness in a mouse model of allergic asthma, according to a report in the May 1st issue of the Journal of Immunology.
IL-4 and IL-13 play both overlapping and independent roles in allergic asthma, the authors explain, and agents that block the IL-4/IL-13 complex may provide benefits not afforded by blocking either receptor alone.
Dr. Erwin W. Gelfand, from the National Jewish Medical and Research Center in Denver, Colorado, and colleagues developed a murine IL-4 mutant (mIL-4Ra) that binds to the IL-4 receptor with high affinity but without activating cellular responses. In the mouse model, mIL-4Ra inhibited cellular responses to both IL-4 and IL-13 stimulation, as well as inhibiting IL-4- and IL-13-induced IgE production.
In mice sensitized to and stimulated with ovalbumin, mIL-4Ra significantly reduced airway hyperresponsiveness, reduced the number of inflammatory cells in the airways, and diminished the hyperproduction of mucus, according to the report.
Administration of mIL-4Ra also inhibited increases in IL-4, IL-5 and IL-13 in the airways of sensitized mice and, during ovalbumin challenge, inhibited the development of the usual IgE response, the researchers note.
J Immunol 2001;166:5792-5800. |
