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

MG Chiaramonte, LR Schopf, TY Neben… - The Journal of …, 1999 - journals.aai.org
MG Chiaramonte, LR Schopf, TY Neben, AW Cheever, DD Donaldson, TA Wynn
The Journal of Immunology, 1999journals.aai.org
Schistosoma mansoni egg-induced pulmonary granuloma formation is a cell-mediated
inflammatory response associated with dominant Th2-type cytokine expression, tissue
eosinophilia, and high levels of serum IgE. In the present study, we show that in vivo
blockade of the Th2 cytokine IL-13, using soluble IL-13R α2-Fc fusion protein, significantly
reduced the size of pulmonary granulomas in unsensitized as well as egg-sensitized mice.
Blocking IL-13 also significantly reduced total serum IgE levels. Interestingly, however, IL-13 …
Abstract
Schistosoma mansoni egg-induced pulmonary granuloma formation is a cell-mediated inflammatory response associated with dominant Th2-type cytokine expression, tissue eosinophilia, and high levels of serum IgE. In the present study, we show that in vivo blockade of the Th2 cytokine IL-13, using soluble IL-13R α2-Fc fusion protein, significantly reduced the size of pulmonary granulomas in unsensitized as well as egg-sensitized mice. Blocking IL-13 also significantly reduced total serum IgE levels. Interestingly, however, IL-13 blockade did not affect the evolving egg-induced Th2-type cytokine response. IL-4, IL-5, as well as IL-13 responses were indistinguishable in control-Fc-and soluble IL-13R α2-Fc fusion protein-treated animals. The smaller granulomas were also phenotypically like the control Fc-treated mice, displaying a similar eosinophil content. Additional studies in IL-4-deficient mice demonstrated that IL-13 was produced, but at much lower levels than in wild-type mice, while IL-4 expression was completely independent of IL-13. Moreover, while granuloma formation was partially reduced in IL-4-deficient mice, blocking IL-13 in these animals almost completely abrogated granuloma development and the pulmonary eosinophilia, while it simultaneously increased IFN-γ production. Together, these data demonstrate that IL-13 serves as an important mediator of Th2-mediated inflammation and plays a role in eliciting IgE responses triggered by schistosome eggs.
journals.aai.org