IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs
| Autor: | M G, Chiaramonte, L R, Schopf, T Y, Neben, A W, Cheever, D D, Donaldson, T A, Wynn |
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| Rok vydání: | 1999 |
| Předmět: |
Interleukin-13
Granuloma Respiratory Tract Lung Diseases Parasitic Recombinant Fusion Proteins Receptors Interleukin-13 Receptors Interleukin Immunoglobulin E Interleukin-13 Receptor alpha1 Subunit Schistosomiasis mansoni Immunoglobulin Fc Fragments Immunophenotyping Up-Regulation Eosinophilic Granuloma Mice Inbred C57BL Interferon-gamma Kinetics Mice Th2 Cells Solubility Animals Female Interleukin-4 Ovum |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 162(2) |
| ISSN: | 0022-1767 |
| Popis: | 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 alpha2-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 alpha2-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-gamma 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. |
| Databáze: | OpenAIRE |
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