IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs

Schistosoma mansoni egg-induced pulmonary granuloma formation is a cell-med iated inflammatory response associated with dominant Th2-type cytokine expr ession, tissue eosinophilia, and high levels of serum IgE, In the present s tudy, we show that in vivo blockade of the Th2 cytokine IL-13, using solubl e IL-13R alpha 2-Fc fusion protein, significantly reduced the size of pulmo nary granulomas in unsensitized as well as egg-sensitized mice. Blocking IL -13 also significantly reduced total serum IgE levels. Interestingly, howev er, IL-13 blockade did not affect the evolving egg-induced Th2-type cytokin e response. IL-4, IL-5, as well as IL-13 responses were indistinguishable i n control-Fc- and soluble IL-13R alpha 2-Fc fusion protein-treated animals. The smaller granulomas were also phenotypically like the control Fc-treate d mice, displaying a similar eosinophil content. Additional studies in IL-4 -deficient mice demonstrated that IL-13 was produced, but at much lower lev els than in wild-type mice, while IL-4 expression was completely independen t of IL-13, Moreover, while granuloma formation was partially reduced in IL -4-deficient mice, blocking IL-13 in these animals almost completely abroga ted granuloma development and the pulmonary eosinophilia, while it simultan eously increased IFN-gamma production. Together, these data demonstrate tha t IL-13 serves as an important mediator of Th2-mediated inflammation and pl ays a role in eliciting IgE responses triggered by schistosome eggs.