THE harmful fibrosis which often occurs in the context of infectious.
disease involves the excessive deposition of connective tissue matrix,
particularly collagen, and is mostly resistant to pharmacological and
immunological intervention(1). In schistosomiasis, fibrosis is associ
ated with the granulomatous response to parasite eggs trapped in the l
iver(2). We have previously shown that interleukin (IL)-12 administere
d peritoneally with eggs prevents subsequent pulmonary granuloma forma
tion on intravenous challenge with eggs(3). Here we show that sensitiz
ation with eggs plus IL-12 partly inhibits granuloma formation and dra
matically reduces the tissue fibrosis induced by natural infection wit
h Schistosoma mansoni worms. These results are an example of a vaccine
against parasites which acts by preventing pathology rather than infe
ction. IL-12, is known to favour the priming of Th1 rather than Th2 ce
lls, and the effects on fibrosis are accompanied by replacement of the
Th2-dominated pattern of cytokine expression characteristic of S. man
soni infection with one dominated by Th1 cytokines. Elevated Th2 cytok
ine expression and fibrosis are common manifestations of a wide variet
y of infectious diseases and atopic disorders which might be ameliorat
ed by vaccination with antigen and IL-12.