Suppression of Immunopathology in Schistosomiasis by Interleukin-2-Targeted Fusion Toxin, DAB389IL-2 I. Studies ofin Vitroandin VivoEfficacy

Schistosomiasis causes pathology in an estimated 200 million individuals. Clinical disease is caused by a complex immunopathologic response to the parasite ova, which are deposited in the host tissues. This immunopathologic response is caused by T lymphocytes which express the high-affinity IL-2 receptor (IL-2R). DAB389IL-2 is a diphtheria toxin-IL-2 fusion toxin protein which functionally inactivates or kills cells which bear the high-affinity IL-2R. DAB389IL-2 has been used in man to suppress IL-2R-dependent immune reactivity. Therefore, we reasoned that DAB389IL-2 might suppress immunopathology in schistosomiasis. In these studies we assessed thein vitroandin vivoeffects of DAB389IL-2 on the development of immunopathology in murine schistosomiasis. DAB389IL-2 suppressed IL-2, lectin mitogen (Con A), and solubleSchistosoma mansoniegg antigen-induced lymphocyte proliferation andin vitrogranuloma formation. In addition, DAB389IL-2 suppressedin vitroIL-2R expression. DAB389IL-2 also suppressed the development of granulomas and collagen depositionin vivoin the livers of infected animals. Therefore, DAB389IL-2 may have potential for the targeted reduction of immunopathology due to schistosomiasis in man.