RESUMEN
Background: Schistosomal hepatic periportal fibrosis, which affects 5-10% of individuals infected with Schistosoma mansoni, is caused by the T-cell-dependent granuloma that develops 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 individuals
Aim: The goal of the present study was to evaluate interferon gamma [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha] in sera obtained from a large number of individuals with different degrees of schistosomal hepatic fibrosis, relate them to fibrosis levels determined by echography, and correlate them with age and sex of the patients
Patients and methods: IFN-gamma and TNF-alpha levels in the sera of 80 patients [49 male and 31 female patients] with S. mansoni infection were determined by means of enzyme-linked immunosorbent assay. Periportal fibrosis as defined by ultrasound examination was graded from F-0 to F-III. Each grade included 20 patients. The relation of age and sex to fibrosis intensity and serum levels of IFN-gamma and TNF-alpha was studied
Results: Levels of IFN-gamma in the sera of patients with no [F-0] or mild [F-I] fibrosis were significantly higher than those of patients with moderate [F-II] or severe [F-III] fibrosis [mean +/- SD in pg/ml for groups F-0, F-I, F-II, and F-III, respectively: 70.3 +/- 13.5, 72.01 +/- 14.5, 60.7 +/- 11.9, and 55.7 +/- 15.6]. Similar results were obtained when comparing male patients alone or female patients alone. In contrast, levels of TNF-alpha in the sera of patients with severe [F-III] or moderate [F-II] fibrosis were significantly higher than those found in patients with mild [F-I] or no [F-0] fibrosis [mean +/- SD in pg/ml for groups F-III, F-II, F-I, and F-0, respectively: 130.4 +/- 11.4, 126.3 +/- 13.9, 115.5 +/- 12.9, and 108.9 +/- 15.4]. However, in male patients they were significantly higher in those at F-III and F-II, whereas in female patients they were not. The prevalence of fibrosis at different grades was uniform in male patients, independent of age, whereas female patients had moderate and severe fibrosis at more advanced ages
Conclusion: Serum levels of IFN-gamma are elevated in patients with no or mild fibrosis irrespective of sex, whereas serum levels of TNF-alpha are elevated in patients with extensive fibrosis only among male patients. Severe fibrosis in female patients occurs at advanced age and has no relation to TNF-alpha levels. The results strongly suggest that IFN-gamma plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-alpha may aggravate the disease, especially in male patients