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*
Division of Infectious Diseases, Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya;
Department of Physiology, Division of Comparative Medicine, Biomedical Center, Uppsala University, Uppsala, Sweden; and
Division of Geographic Medicine, Case Western Reserve University, Cleveland, OH 44106
Recently, we observed that repeated Schistosoma
mansoni infection and treatment boost Th2-associated cytokines
and TGF-ß production in baboons. Other studies have shown that some
chronically infected baboons develop hepatic fibrosis. Because TGF-ß,
IL-2, and IL-4 have been shown to participate in development of
fibrosis in murine schistosomiasis, the present study examined whether
repeated exposure stimulates hepatic fibrosis in olive baboons. To test
this hypothesis, animals were exposed to similar numbers of S.
mansoni cercariae given once or repeatedly. After 19 wk of
infection, animals were cured with praziquantel and reinfected once or
multiple times. Hepatic granulomatous inflammation and fibrosis were
assessed from serial liver biopsies taken at weeks 6, 9, and 16 after
reinfection and egg Ag (schistosome egg Ag)-specific cytokine
production by PBMC were measured simultaneously. Periportal fibroblast
infiltration and extracellular matrix deposition (fibrosis),
angiogenesis, and biliary duct hyperplasia developed in some animals.
The presence and amount of fibrosis directly correlated with the
frequency of exposure. Fibrosis was not associated with adult worm or
tissue egg burden. The amount of fibrosis correlated with increased
schistosome egg Ag-driven TGF-ß at 6, 9, and 16 wk postinfection
(rs = 0.9, 0.8, and 0.54, respectively,
all p < 0.01) and IL-4 production
(p = 0.02) at 16 wk postinfection and not IFN-
,
IL-2, IL-5, or IL-10. These data suggest that repeated exposure is a
risk factor for periportal fibrosis by a mechanism that primes
lymphocytes to produce increased levels of profibrotic molecules that
include TGF-ß and IL-4.
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