{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:55:22Z","timestamp":1790898922110,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2002,7,1]],"date-time":"2002-07-01T00:00:00Z","timestamp":1025481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hepatic periportal fibrosis, which affects 5\u201310% 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 \u2264 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-\u03b3 levels were associated with a marked reduction of the risk of fibrosis (p = 0.01; OR, 0.1); in contrast, high TNF-\u03b1 levels were associated with an increased risk (p = 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-\u03b3 production. These results with observations in experimental models strongly suggest that IFN-\u03b3 plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-\u03b1 may aggravate the disease.<\/jats:p>","DOI":"10.4049\/jimmunol.169.2.929","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T02:54:25Z","timestamp":1398048865000},"page":"929-936","source":"Crossref","is-referenced-by-count":155,"title":["Cytokine Regulation of Periportal Fibrosis in Humans Infected with <i>Schistosoma mansoni<\/i>: IFN-\u03b3 Is Associated with Protection Against Fibrosis and TNF-\u03b1 with Aggravation of Disease"],"prefix":"10.1093","volume":"169","author":[{"given":"Sandrine","family":"Henri","sequence":"first","affiliation":[{"name":"Immunologie et Ge\u0301ne\u0301tique des Maladies Parasitaires, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 399 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Chevillard","sequence":"additional","affiliation":[{"name":"Immunologie et Ge\u0301ne\u0301tique des Maladies Parasitaires, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 399 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Mergani","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine and Molecular Biology, University of Gezira , Wad Medani ,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Paris","sequence":"additional","affiliation":[{"name":"Immunologie et Ge\u0301ne\u0301tique des Maladies Parasitaires, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 399 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Gaudart","sequence":"additional","affiliation":[{"name":"Immunologie et Ge\u0301ne\u0301tique des Maladies Parasitaires, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 399 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Camilla","sequence":"additional","affiliation":[{"name":"Immunotech , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u0301lia","family":"Dessein","sequence":"additional","affiliation":[{"name":"Immunologie et Ge\u0301ne\u0301tique des Maladies Parasitaires, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 399 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Montero","sequence":"additional","affiliation":[{"name":"Immunotech , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasr-Eldin M A","family":"Elwali","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine and Molecular Biology, University of Gezira , Wad Medani ,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman K","family":"Saeed","sequence":"additional","affiliation":[{"name":"Blue Nile Research Institute , Wad Medani ,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubarak","family":"Magzoub","sequence":"additional","affiliation":[{"name":"Institute of Nuclear Medicine and Molecular Biology, University of Gezira , Wad Medani ,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain J","family":"Dessein","sequence":"additional","affiliation":[{"name":"Immunologie et Ge\u0301ne\u0301tique des Maladies Parasitaires, Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unite\u0301 399 , Marseille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,7,15]]},"reference":[{"key":"2025032905524809000_R1","first-page":"41","volume-title":"Acta Trop.","year":"2000"},{"key":"2025032905524809000_R2","first-page":"268","volume-title":"Lab. 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