Therapeutic effect of IL-13 immunoneutralization during chronic experimental fungal asthma

IL-13 and IL-4 are key contributors to the asthmatic phenotype. The tempora l role of these cytokines in airway function, inflammation, and remodeling were assessed in a chronic murine model of Asperigillus fumigatus-induced a llergic asthma. IL-13 and IL-4 protein levels were significantly elevated b y 30 days after conidia challenge in A. fumigatus-sensitized mice. Furtherm ore, IL-13 alpha1 mRNA expression was significantly elevated 7 days after c onidia challenge and remained elevated until day 21. In contrast, IL-13R al pha2 mRNA expression, although constitutively expressed in naive lung, was absent in the lungs of A. fumigatus-sensitized mice both before and after c onidia challenge. Membrane-bound IL-4R mRNA expression was significantly el evated 7 days after conidia challenge; however, soluble IL-4R mRNA expressi on was increased 30 days after conidia challenge. Immunoneutralization of I L-13 between days 14 and 30 or days 30 and 38 after fungal sensitization an d challenge significantly attenuated airway byperresponsiveness, collagen d eposition, and goblet cell hyperplasia at day 38 after conidia challenge; h owever, the effects of IL-4 immunoneutralization during the same time perio ds were not as marked. IFN-T and IL-12 release after Aspergillus Ag restimu lation was elevated from spleen cells Isolated from mice treated with IL-4 anti-serum compared with IL-13 anti-serum or normal rabbit serum-treated mi ce. This study demonstrates a pronounced therapeutic effect of IL-13-immuno neutralization at extended time points following the induction of chronic a sthma. Most importantly, these therapeutic effects were not reversed follow ing cessation of treatment, and IL-13 anti-serum treatment did not alter th e systemic immune response to Ag restimulation, unlike IL-4 immunoneutraliz ation. Therefore, IL-Q provides an attractive therapeutic target inallergic asthma.