Abstract
THE harmful fibrosis which often occurs in the context of infectious disease involves the excessive deposition of connective tissue matrix, particularly collagen, and is mostly resistant to pharmacological and immunological intervention1. In schistosomiasis, fibrosis is associated with the granulomatous response to parasite eggs trapped in the liver2. We have previously shown that inter-leukin (IL)-12 administered peritoneal!v with eggs prevents subsequent pulmonary granuloma formation on intravenous challenge with eggs3. Here we show that sensitization with eggs plus IL-12 partly inhibits granuloma formation and dramatically reduces the tissue fibrosis induced by natural infection with Schistosoma mansoni worms. These results are an example of a vaccine against parasites which acts by preventing pathology rather than infection. IL-12 is known to favour the priming of Thl rather than Th2 cells, and the effects on fibrosis are accompanied by replacement of the Th2-dominated pattern of cytokine expression characteristic of S. mansoni infection with one dominated by Thl cytokines. Elevated Th2 cytokine expression and fibrosis are common manifestations of a wide variety of infectious diseases and atopic disorders which might be ameliorated by vaccination with antigen and IL-12.
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Wynn, T., Cheever, A., Jankovic, D. et al. An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature 376, 594–596 (1995). https://doi.org/10.1038/376594a0
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DOI: https://doi.org/10.1038/376594a0
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