Interleukin-13 fusion cytotoxin arrests Schistosoma mansoni egg-induced pulmonary granuloma formation in mice.
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.
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000469:parasitology / Q000473:pathology; D005786:Gene Expression Regulation; D018793:Interleukin-13 / Q000235:genetics / Q000494:pharmacology*; D015847:Interleukin-4 / Q000235:genetics; D008168:Lung / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D010063:Ovum; D016726:Plasma Cell Granuloma, Pulmonary / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D011347:Procollagen / Q000235:genetics; D011549:Pseudomonas; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control
D001426:Bacterial Proteins; D024061:Collagen Type III; D018793:Interleukin-13; D011347:Procollagen; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D003094:Collagen