In vitro and in vivo pharmacological assessment of a targeted plasmid gene containing immunotoxin, DT390-IL-18-SRα on suppression of immunopathology in mice experimentally infected with Shistosoma mansoni (P4192)

Abstract

Abstract Purpose: To evaluate both in vitro and in vivo effects of DT390-IL-18-SRα immunotoxoin on the development of liver immunopathology in murine schistosomiasis mansoni. Methods: The antiproliferative effect and in vitro granuloma formation (IVGF) inhibition were evaluated using methyl thaiazolyl tetrazolium and IVGF index respectively. In vivo evaluation, mice were divided into four groups of twelve mice each: Group1 normal non infected (-ve control), Group 2, 3 and 4 were infected percutaneously with 25 cercariae. After 6 weeks post infection, Group2 was treated with PBS (+ve control), Group3 was treated with plasmid DNA (50 µg) embedded with cationic liposome in 50 µl PBS, injected intramuscular in the hind limbs once daily for two weeks and Group4 was treated with DT390-SRα (mutant control). After animals sacrification, liver was removed for histopathological studies. Results: DT390-IL-18-SRα showed suppression of spleen lymphocytes proliferation and IVGF in a dose dependant manner as well as suppression of liver granulomas size by 80%, while mutant toxin had no significant suppression. Conclusion: The immunotoxin showed selective toxicity to antigen activated lymphocytes in vitro with reduced clinical and pathological severities of the disease.