Abstract
Schistosoma mansoni egg-induced lung pathology requires the actions of interleukin (IL)-4 and IL-13. Because receptors for IL-4 and IL-13 share chains, we examined the effect of a fusion protein comprised of IL-13 and Pseudomonas exotoxin (IL13-PE) on the development of pulmonary granulomas in mice. At day 8 after an intravenous injection of live S. mansoni eggs, whole lung samples from IL13-PE-treated mice exhibited significantly lower IL-4 and IL-13 gene expression, smaller granulomas, decreased collagen levels, and increased IL-13 receptor alpha2 gene expression compared to controls. The therapeutic effects of IL13-PE were also observed at day 16 despite the termination of IL13-PE treatment at day 8. These studies demonstrate that targeting IL-4- and IL-13- responsive cells with IL13-PE effectively arrests S. mansoni egg granuloma formation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bacterial Proteins / pharmacology
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Cells, Cultured
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Collagen / genetics
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Collagen Type III / genetics
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Disease Models, Animal
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Female
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Fibroblasts / parasitology
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Fibroblasts / pathology
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Gene Expression Regulation
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Interleukin-13 / genetics
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Interleukin-13 / pharmacology*
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Interleukin-4 / genetics
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Lung / parasitology
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Lung / pathology*
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Mice
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Mice, Inbred CBA
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Ovum*
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Plasma Cell Granuloma, Pulmonary / parasitology
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Plasma Cell Granuloma, Pulmonary / pathology
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Plasma Cell Granuloma, Pulmonary / prevention & control*
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Procollagen / genetics
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Pseudomonas
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Recombinant Fusion Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Schistosoma mansoni / pathogenicity*
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Schistosomiasis mansoni / immunology*
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Schistosomiasis mansoni / pathology
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Schistosomiasis mansoni / prevention & control
Substances
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Bacterial Proteins
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Collagen Type III
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Interleukin-13
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Procollagen
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Recombinant Fusion Proteins
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Interleukin-4
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Collagen