Ip. Oswald et al., IL-12 INHIBITS TH2 CYTOKINE RESPONSES INDUCED BY EGGS OF SCHISTOSOMA-MANSONI, The Journal of immunology, 153(4), 1994, pp. 1707-1713
In the mouse, infection with the helminth parasite Schistosoma mansoni
results in the selective induction of CD4(+) T lymphocytes belonging
to the Th2 subset. Schistosome ova are responsible for the development
of Th2 responses seen in patently infected animals and the injection
of eggs s.c. into the footpad leads to the development of elevated Th2
cytokine production by T cells in the draining popliteal lymph node.
Using the egg injection model, we have shown that IL-12 suppresses sch
istosome egg-induced Th2 responses as evidenced by decreased IL-4, IL-
5, and IL-10 secretion in vitro while increasing the production of the
Th1 cytokine IFN-gamma. Similar responses were obtained using either
total lymph node cells or purified CD4(+) T cells, indicating that IL-
12 acts at the T cell level. When given as a single injection IL-12 wa
s most effective at inhibiting Th2 responses when administered 2 days
after egg inoculation, a time when T cells are still in a Th0 phase. T
he suppression of Th2 responses induced by IL-12 was blocked when the
animals were simultaneously injected with neutralizing anti-IFN-gamma
mAb, either systemically or systemically plus locally. Anti-IFN-gamma
also inhibited the enhancement of IFN-gamma responses induced by IL-12
but only if the mAb was administered systemically plus locally. NK ce
lls are likely to be a major source of the immunoregulatory IFN-gamma,
because the effects of IL-12 on Th2 cytokine production were suppress
ed in mice treated with anti-asialo-GM1 Abs. Together these results su
ggest that IL-12 may have potential use in preventing or treating para
site-induced pathology resulting from Th2 cytokine production.