In work completed this year, endothelial cells were shown to be activated by cytokines to kill schistosomula in culture. This effector mechanism was shown to require the production of nitrogen oxides and to be inhibitable by IL-4. An in vivo role for endothelial effector cells was suggested by the altered morphology of pulmonary endothelium in vaccinated mice rejecting challenge infections and the elevated expression of NO synthase mRNA. Studies on the regulation of egg pathology in mice indicated that INF- gamma downregulates both egg-specific Th2 cytokine response and granuloma formation. NK cells were implicated as the endogenous source of the INF- gamma. IL-12, through its induction of INF-gamma, was shown to be a potent down-regulator of granuloma formation in both liver and lung. In a field study performed in Recife, Brazil, PBMC from patients infected with S. mansoni were shown to produce a predominant TH2 cytokine response to parasite antigens and mitogens, with minimal TH1 responses displayed to egg antigens. In this respect, the human cytokine response was found to closely resemble that previously described by us in mice.
