Ta. Wynn et al., ELEVATED EXPRESSION OF TH1 CYTOKINES AND NITRIC-OXIDE SYNTHASE IN THELUNGS OF VACCINATED MICE AFTER CHALLENGE INFECTION WITH SCHISTOSOMA-MANSONI, The Journal of immunology, 153(11), 1994, pp. 5200-5209
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.