ELEVATED EXPRESSION OF TH1 CYTOKINES AND NITRIC-OXIDE SYNTHASE IN THELUNGS OF VACCINATED MICE AFTER CHALLENGE INFECTION WITH SCHISTOSOMA-MANSONI

C57BL/6 mice were vaccinated with irradiated cercariae of Schistosoma mansoni, and, at various times after challenge infection, total lung m RNA was isolated to assess the induction of several cytokines that pre viously had been shown in in vitro studies to be involved in the activ ation of macrophages and/or endothelial cells for nitric oxide (NO) pr oduction and killing of schistosomula. Vaccinated mice demonstrated a highly significant increase in lFN-gamma mRNA upon subsequent infectio n when compared with infected nonvaccinated controls. A similar, altho ugh less dramatic, increase in two other macrophage-activating cytokin es, TNF-alpha and IL-2, also was observed. In contrast, although the T h2 cytokines IL-4, IL-5, IL-10, and IL-13 were elevated in challenged vaccinated animals, only IL-10 and IL-13 showed increases that were si gnificant with respect to the mRNA levels observed in challenged contr ols. Neutralization of IFN-gamma reduced immunity in vaccinated animal s and resulted in decreased IFN-gamma, IL-2, IL-10, TNF-alpha, and IL- 12 p40 but markedly increased IL-4, IL-5, and IL-13 mRNA expression an d serum IgE levels. Pulmonary NO synthase expression was elevated in i mmunized mice at a time at which immune elimination of schistosomula i s believed to occur. Moreover, suppression of NO synthase activity wit h the inhibitor aminoguanidine reduced immunity, as measured by a 32 t o 33% increase in worm burden. Together, these data support previous i n vitro studies that suggest a role for NO in schistosomulum killing. Furthermore, the observation that the down-regulatory cytokines IL-4, IL-10, and IL-13 are induced together with IFN-gamma may provide an ex planation for the failure of this vaccine to provide complete protecti on.