AN IL-12-BASED VACCINATION METHOD FOR PREVENTING FIBROSIS INDUCED BY SCHISTOSOME INFECTION

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.