An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response

J Clin Invest. 1999 Sep;104(6):777-85. doi: 10.1172/JCI7325.


In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to tissue destruction and fibrosis, which causes much of the morbidity and mortality associated with this disease. Here we show the importance of IL-13 in the pathogenesis of schistosomiasis, and demonstrate, perhaps for the first time, the therapeutic efficacy of an IL-13 inhibitor, sIL-13Ralpha2-Fc, in the control of hepatic fibrosis. T-helper type 2 (Th2) cytokines dominate the immune response in mice infected with Schistosoma mansoni, yet the specific contributions of IL-13 and IL-4 to the development of fibrosis were not previously investigated. Our studies demonstrate that both cytokines play redundant roles in granuloma formation, which explains the ability of IL-4-deficient mice to form granulomas around eggs. More importantly, however, these studies demonstrate that IL-13 is the dominant Th2-type cytokine regulating fibrosis. IL-13 stimulated collagen production in fibroblasts, and procollagen I and procollagen III mRNA expression was decreased in sIL-13Ralpha2-Fc-treated mice. Moreover, the reduction in fibrosis observed in IL-4-deficient mice was much less pronounced than that in sIL-13Ralpha2-Fc-treated animals. Fibrosis is a major pathological manifestation of a number of allergic, autoimmune, and infectious diseases. Thus, our findings provide evidence that IL-13 inhibitors may be of general therapeutic benefit in preventing damaging tissue fibrosis resulting from Th2-dominated inflammatory responses.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Female
  • Interleukin-13 / antagonists & inhibitors*
  • Interleukin-4 / deficiency
  • Liver / metabolism
  • Liver Cirrhosis, Experimental / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Procollagen / genetics
  • RNA, Messenger / analysis
  • Schistosomiasis mansoni / complications
  • Schistosomiasis mansoni / immunology
  • Schistosomiasis mansoni / therapy*
  • Th1 Cells / immunology
  • Th2 Cells / immunology*


  • Cytokines
  • Interleukin-13
  • Procollagen
  • RNA, Messenger
  • Interleukin-4