Suppression of immunopathology in schistosomiasis by interleukin-2-targeted fusion toxin, DAB389IL-2. I. Studies of in vitro and in vivo efficacy.
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 the in vitro and in vivo effects of DAB389IL-2 on the development of immunopathology in murine schistosomiasis. DAB389IL-2 suppressed IL-2, lectin mitogen (Con A), and soluble Schistosoma mansoni egg antigen-induced lymphocyte proliferation and in vitro granuloma formation. In addition, DA-B389IL-2 suppressed in vitro IL-2R expression. DA-B389IL-2 also suppressed the development of granulomas and collagen deposition in vivo in the livers of infected animals. Therefore, DAB389IL-2 may have potential for the targeted reduction of immunopathology due to schistosomiasis in man.
D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D000939:Epitopes; D006099:Granuloma / Q000209:etiology / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D008109:Liver Diseases, Parasitic / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D011993:Recombinant Fusion Proteins; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology* / Q000628:therapy
D000947:Antigens, Helminth; D004167:Diphtheria Toxin; D000939:Epitopes; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D003208:Concanavalin A; C078456:denileukin diftitox