Schistosoma mansoni infections are associated with a strong
Th2 cytokine response. Treatment of mice with IL-12 or anti-IL-2
or anti-IL-4 before i.v. injection of eggs increased
IFNγ production and downregulated Th2
responses and pulmonary granuloma size. Conversely, anti-IFN-γ antibody treatment increased Th2
responses and granuloma size. Similar manipulation produced less
dramatic results in infected mice. However, sensitization
of mice with eggs + IL-12 before infection augmented the Th1
response and decreased Th2 cytokines, granuloma size and
fibrosis. Antisera to IFNγ, TNFα or IL-12 during IL-12-egg immunization
partly restored granuloma size and fibrosis following infection.
Variations in the size of granulomas in acute (8 week)
infections may be influenced primarily by the number and state of
activation of T cells. In chronic (12-16 week) infections
immunologic downmodulation proceeded normally in mice without
functional CD8+ cells and in IFNγ KO
mice but not in B cell KO (mMT) mice or in mice deficient in FcR
expression in spite of the fact that these mice downregulated
their T cell and cytokine responses. It is evident that the
participation of cytokines in granuloma formation and regulation
is complicated and that the mechanisms controlling both these
phenomena are likely to involve both T cells and antibody/FcR
interactions.
