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Is Associated with Protection Against Fibrosis and TNF-
with Aggravation of Disease1
* Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Unité 399, Marseille, France;
Institute of Nuclear Medicine and Molecular Biology, University of Gezira, Wad Medani, Sudan;
Immunotech, Marseille, France; and
Blue Nile Research Institute, Wad Medani, Sudan
Hepatic periportal fibrosis, which affects 5–10% of subjects
infected by Schistosoma mansoni, is caused by the T
cell-dependent granuloma that develop around schistosome eggs.
Experimental models of infection have shown that granuloma and fibrosis
are tightly regulated by cytokines. However, it is unknown why advanced
periportal fibrosis occurs only in certain subjects. The goal of the
present study was to evaluate the cytokine response of S.
mansoni-infected subjects with advanced liver disease in an
attempt to relate susceptibility to periportal fibrosis with an
abnormal production of cytokines that regulate granuloma and fibrosis.
Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese
village in which S. mansoni is endemic: advanced
periportal fibrosis was observed in 12% of the population; 35% of the
affected subjects exhibited signs of portal hypertension. Age (odds
ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2)
were significantly (p 
0.01) associated with
hepatic fibrosis. Cytokines produced by egg-stimulated blood
mononuclear cells from 99 subjects were measured (75 with no or mild
fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of
cytokine levels showed that high IFN-
levels were associated with a
marked reduction of the risk of fibrosis (p = 0.01;
OR, 0.1); in contrast, high TNF-
levels were associated with an
increased risk (p = 0.05; OR, 4.6) of periportal
fibrosis. Moreover, infection levels were negatively associated with
IFN- production. These results with observations in experimental
models strongly suggest that IFN- plays a key role in the protection
of S. mansoni-infected patients against periportal
fibrosis, whereas TNF- may aggravate the
disease.
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