IL-11 and
IL-11 receptor (R)alpha are induced by Th2
cytokines. However, the role(s) of endogenous
IL-11 in
antigen-induced Th2
inflammation has not been fully defined. We hypothesized that
IL-11, signaling via IL-11Ralpha, plays an important role in aeroallergen-induced Th2
inflammation and mucus
metaplasia. To test this hypothesis, we compared the responses induced by the aeroallergen
ovalbumin (OVA) in wild-type (WT) and IL-11Ralpha-null mutant mice. We also generated and defined the effects of an antagonistic
IL-11 mutein on pulmonary Th2 responses. Increased levels of
IgE, eosinophilic tissue and bronchoalveolar lavage (BAL)
inflammation,
IL-13 production, and increased mucus production and secretion were noted in OVA-sensitized and -challenged WT mice. These responses were at least partially
IL-11 dependent because each was decreased in mice with null mutations of IL-11Ralpha. Importantly, the administration of the
IL-11 mutein to OVA-sensitized mice before
aerosol antigen challenge also caused a significant decrease in OVA-induced
inflammation, mucus responses, and
IL-13 production. Intraperitoneal administration of the mutein to lung-specific IL-13-overexpressing transgenic mice also reduced BAL
inflammation and airway mucus elaboration. These studies demonstrate that endogenous IL-11R signaling plays an important role in
antigen-induced sensitization, eosinophilic
inflammation, and airway mucus production. They also demonstrate that Th2 and
IL-13 responses can be regulated by interventions that manipulate
IL-11 signaling in the murine lung.