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 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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Eosinophilic Granuloma / immunology
-
Eosinophilic Granuloma / prevention & control
-
Female
-
Granuloma, Respiratory Tract / immunology*
-
Granuloma, Respiratory Tract / pathology
-
Granuloma, Respiratory Tract / prevention & control
-
Immunoglobulin E / biosynthesis*
-
Immunoglobulin E / blood
-
Immunoglobulin Fc Fragments / genetics
-
Immunoglobulin Fc Fragments / pharmacology
-
Immunophenotyping
-
Interferon-gamma / biosynthesis
-
Interleukin-13 / antagonists & inhibitors
-
Interleukin-13 / biosynthesis
-
Interleukin-13 / immunology*
-
Interleukin-13 / metabolism
-
Interleukin-13 Receptor alpha1 Subunit
-
Interleukin-4 / deficiency
-
Interleukin-4 / genetics
-
Kinetics
-
Lung Diseases, Parasitic / immunology*
-
Lung Diseases, Parasitic / pathology
-
Lung Diseases, Parasitic / prevention & control
-
Mice
-
Mice, Inbred C57BL
-
Ovum / immunology*
-
Receptors, Interleukin / genetics
-
Receptors, Interleukin / physiology
-
Receptors, Interleukin-13
-
Recombinant Fusion Proteins / pharmacology
-
Schistosomiasis mansoni / immunology*
-
Schistosomiasis mansoni / pathology
-
Schistosomiasis mansoni / prevention & control
-
Solubility
-
Th2 Cells / immunology*
-
Th2 Cells / metabolism
-
Th2 Cells / parasitology
-
Up-Regulation / immunology
Substances
-
Il13ra1 protein, mouse
-
Immunoglobulin Fc Fragments
-
Interleukin-13
-
Interleukin-13 Receptor alpha1 Subunit
-
Receptors, Interleukin
-
Receptors, Interleukin-13
-
Recombinant Fusion Proteins
-
Interleukin-4
-
Immunoglobulin E
-
Interferon-gamma