Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis.

摘要: Abstract In several allergic, autoimmune, and infectious diseases, fibrosis is a major cause of morbidity mortality. Here, using model infection-induced liver fibrosis, we show that interleukin (IL)-13 required at all stages Schistosomiasis mansoni infection to induce fibrosis. IL-4 production was preserved in IL-13–deficient mice, yet failed significantly contribute the fibrotic response either acute or chronic infection. Significant develops infected although magnitude varies widely inbred mice. C3H/HeN, BALB/c, C57BL/6 mice develop high, intermediate, low levels respectively. Despite these differences, IL-13 antagonism resulted marked amelioration strains. The mechanism high- low-responder strains unrelated their tissue eosinophil mast cell responses, but did correlate with patterns IL-13, IL-10, interferon gamma (IFN-γ) mRNA expression. Indeed, severe correlated high IFN-γ/IL-10 response. Because diseases are typically progressive disorders, an important issue determine whether inactivation might be used treat established ongoing disease. highly efficacious, even after Th2 cytokine were firmly established. These studies demonstrate central role played by fibrogenesis suggest therapeutic approaches aimed disrupting pathway will effective preventing disease caused Th2-mediated inflammatory reactions. (H EPATOLOGY 2001;34:273-282.)