Immunoregulation of granuloma formation and fibrosis in schistosomiasis by antigen-daunomycin immunoconjugate II-in vivo studies

ABSTRACT

Hepatic granuloma formation and fibrosis in schistosomiasis are the principle cause of morbidity. These inflammatory responses are induced and regulatd by T-Iymphocytes with receptors for soluble Egg Antigen [SEA]. These T cells are genentically heterogeneous in man. Approaches that avoid genetic restriction by directly addressing antigen and T cell interaction will be useful. During the Present work, SEA [major anti genic stimulus for immunopathology in schistosomiasis] was conjugated to Daunomycin [DM], a cytotoxic rhodamycin. The suppression effects of SEA-DM on the development of granuloma formation and fibrosis due to schistosomiasis mansoni in mice was assessed. Relative to saline treated control group, SEA-DM when administered intravenously, it specifically diminished the liver granulomata size by 65% in infected mice in response to S. mansoni eggs deposited in the liver tissue at the acute stage of the disease [6-8 weeks post-infection]. In addition, SEA-DM reduced the hepatic collagen synthesis by 64% and reduced the deposition of hepatic matrix proteins such as, isotypes I and II collagens and fibronectin. Moreover, SEA- DM suppressed the accummulation of CD[4+] cells [helper cells] within the granulomatous lesions and liver parenchyma, but had little effect on CD[8+] [suppressor cells]. DM alone resulted in 50% mortality and severe morbidity, but there was no visible mortality in the SEADM animal group