regulation of murine schistosome granuloma formation and fibrosis by anti-IL-4 and anti-IL-13 immunotherapy

ABSTRACT

In this study the availability of murine anti-interleukin-4 [anti IL-4] and anti-interleukin- 13[anti-Il- 13] monoclonal antibodies [mAbs] permited the intimate study of the direct role of IL-13 in a type -2-cytokine mediated infection. The present study demonstrates that blocking of IL-13 from the Th -2 response to Schistosoma mansoni infection is beneficial to host survival. This enhanced prognosis correlates with a reduction in hepatic collagen deposition and indicates the role for IL-13 in the development of hepatic fibrosis. In contrast, the study has also showed that blocking of IL-4 results in very high mortality characterized by a breakdown in intestinal integrity, indicating that IL-4- is a protective cytokine in schistosome infection. The combined blocking of both IL-4 and IL-13 demonstrates that the positive effects resulting from the ablation of IL- 13 were over-ridden by the detrimental pathology resulting from IL-4 blocking. In addition, combined cytokine blocking resulted in a condition that was considerably more severe than that observed in the IL-4 blocking group. These results indicate the potential benefits of anti- IL-13 as an antifibrogenic cytokine, but also show the dangers of blocking both IL-13 and IL-4 concurrently