488 Lung delivery of an interleukin-9 antibody treatment inhibits airway hyperresponsiveness (AHR), BAL eosionophila, mucin production, and serum IgE elevation to natural antigens in a murine model of asthma

An Update on Interleukin-9: From Its Cellular Source and Signal Transduction to Its Role in Immunopathogenesis

“…In an animal model of allergic asthma, exposure to Aspergillus fumigatus or a dust mite antigen resulted in an allergic inflammatory response in mice including significant increases in Broncho Alveolar lavage (BAL) eosinophils, high serum IgE levels, increased mucin production, and enhanced AHR. The intratracheal administration of an IL-9-neutralizing antibody reduced the allergic inflammation in these animals [66]. Similar results were obtained with the systematic administration of an IL-9 neutralization antibody in ovalbumin-treated BALB/c mice [67].…”

Th2 cytokines and asthma — Interleukin-9 as a therapeutic target for asthma

“…Intratracheal administration of IL-9-neutralizing antibody reduced the constellation of allergic inflammation in these models including AHR, serum total IgE elevations, and increases in BAL eosinophils in comparison with treatments of isotype-specific control antibody or untreated sensitized mice. Alcian Blue/PAS stains for mucus and overall histopathologic grading confirmed that the antibody treatment effectively abrogated the allergic asthmatic response in the antigen-challenged animals [16]. An independent study showed that similar blockage results from systematic administration of an IL-9 neutralization antibody in ovalbumin-treated BALB/c mice [17].…”

“…Recently, two studies using IL-9 neutralizing antibody confirmed that IL-9 is a necessary mediator of asthma [16,17]. In one of the models, IL-9-neutralizing antibody was instilled directly into the lungs of mice exposed to either Aspergillus fumigatus or dust mite antigen.…”

“…However, the crucial roles of these factors in supporting the normal biology of specific cell types suggest that blocking their activity might compromise normal host defense. Recently, IL-9 and IL-13 have been shown to mediate AHR in the allergic lung, and blockage of either cytokine by using neutralizing antibody or soluble receptor is sufficient to attenuate AHR in selective animal models [12,13,14,15,16,17]. In this review we examine recent evidence supporting a central role for IL-9 as a critical mediator of allergic asthma, comparing these data with similar studies on IL-4, IL-5, and IL-13.…”