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Pentoxifylline (PTX) was proved to exert both anti-inflammatory and anti-fibrotic effects, and was used therapeutically in this experimental model to investigate its role alone or with praziquantel (PZQ) in Schistosoma mansoni-infected mice, and to explore its impact on the tissue expression of transforming growth factor-beta1 (TGF-beta1). S. mansoni-infected mice were divided into seven groups: Control untreated (I), treated with curative dose of PZQ, 500 mg/kg/day for 2 consecutive days (II), or subcurative dose, 100 mg/kg/day for 2 consecutive days (III), treated with PTX (10 mg/kg/day for 5 days/wk) alone for 4 weeks (IV) or in addition to subcurative dose of PZQ (V), and treated with PTX alone for 8 weeks (VI) or in addition to subcurative dose of PZQ (VII). All animals were killed 10 weeks post infection. Parasitological assessment of worm burden, tissue egg load and oogram pattern was carried out. The degree of granulomatous fibrosis and eosinophilic cell population was quantified in Sirius-red-stained sections and tissue transforming growth factor beta-1 expression was estimated immunohistochemically. Serum ALAT and GGT, as well as hepatic content of reduced GSH, were measured. The results revealed the highest percent of worm reduction and dead ova in groups (II) and (VII) accompanied by significant diminution in granulomatous parameters, collagen content and TGF-beta1 tissue expression. Moreover, treatments with PTX and/or PZQ ameliorated the liver functions. In conclusion, prolonged treatment with PTX has a potent anti-fibrogenic role especially when used in the early stages of infection, with limited toxic effects on schistosome worms and eggs. Thus, PTX can be used as an adjuvant therapeutic tool with anti-helminthic drugs in the treatment of human schistosomiasis.

After placement in mice of PZQ-sensitive and -insensitive S. mansoni isolates obtained from villagers responding and not responding to PZQ, parasitological criteria reflecting their biological development and also the host anti-immature worm immunoglobulin isotypes were examined 8 and 10 weeks post infection. Hepatic granuloma diameter, hepatic histopathological changes and immunolocalization of IgG and IgM on the surface of PZQ-sensitive and -resistant worms were also examined 10 weeks post infection. Data showed that parasitological criteria were not significantly different between mice infected with the PZQ-sensitive and -insensitive S. mansoni isolates. As regards serum immunoglobulins, in mice infected with the PZQ-insensitive S. mansoni isolate, IgG and IgG1 were significantly (p<0.05) lower 8 and 10 weeks post infection, respectively (1.41+/-0.07 and 1.08+/-0.10 and 1.35+/-0.06 and 1.09+/-0.07) than in mice infected with the PZQ-sensitive S. mansoni isolate (1.73+/-0.15 and 1.38+/-0.10 and 1.73+/-0.17 and 1.54+0.21) after the same observation periods. IgM level was nearly the same while IgE was lower than that recorded in mice infected with the PZQ-sensitive S. mansoni isolate. IgG immunofluorescence was also lower (60%+/-6.78) on the surface of resistant worms than that of sensitive worms (66.6%+/-5.27); meanwhile, hepatic granuloma diameter was significantly larger (296.5+/-3.0 vs 283.6+/-4.0) in mice infected with the PZQ-insensitive S. mansoni isolate with higher percentage of intact eggs. Differences in the immunogenic make up of PZQ-sensitive and -insensitive S. mansoni isolates qualitatively and/or quantitatively favoring a certain Th cell subpopulation response could be the underlying reason for such differences recorded in the host immunoglobulin isotype response and also the egg-induced hepatic histopathological changes.