An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response.
J Clin Invest
; 104(6): 777-85, 1999 Sep.
Article
em En
| MEDLINE
| ID: mdl-10491413
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquistossomose mansoni
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Células Th2
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Interleucina-13
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Cirrose Hepática Experimental
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos