| Objective:. Studies in mice indicate that S. mansoni egg-induced granuloma formation and hepatic fibrosis (HF) depend markedly on cytokine regulation. How much of the results of work in mice can be extended to S. japonicum in human is unknown. The severity of the disease is a consequence of fibrosis caused by granulomatous reaction around the schistosome eggs that are trapped in the small vessels of the liver. Some subjects who have lived in endemic areas all their life and frequently come into contact with infected water show no clinical manifestations of the disease. Only a small percentage of individuals infected in an area of endemicity actually develop a severe form of the disease. The concentrations of Th1 associated cytokines (IL-10 and IL-13) and Th2 associated cytokines (INF-γand TNF-a) were determined S. japonicum patients serum samples. The concentration compare the patients to the health adult to try find cytokine production and regulation that causes a minority of chronically exposed patients to develop severe HF. Methods:All patients with schistosomiasis came from Dongzhi County in Anhui of China, where S. japonica is highly endemic. Many of them are farmers or fish men. All observed patients had lived in the endemic aerea for 10 years. A total of 358 patients with advanced S. japonica showed positive stool eggs with Kato-Katz method. Among these 358 patients, 83 (23.18%) were HBsAg positive. All the patients were examined by ultrasound (US). Among these patients, 101 (28.2%)were mild HF, 206 (57.5%)were moderate, 51 (14.2%)were severe HF. 68 HBsAg negative patients were chosen randomly as experimental control. Among them, 39(13 to 68 years old) were mild HF(7 males,31 females), 29(35 to 74 years old) were severe HF(11 males,18 females). The sera level of Th1 and Th2 cytokines and hyaluronic acid and laminin were determined . Twenty persons, who came from schistosomiasis-free area in the north of Anhui, were selected as control group. Results: From this survey we found that HBsAg possitive rate were 23.18%, which was significantly higher than the average possitive rate of 10.2% reported in China. Neither earlier nor severer hepatic fibrosis was noted in the patients who had been simultaneously infected with HBV than those only infected with schistosomiasis. Severe hepatic fibrosis has close association with ages but not with the sexes. The level of IL-10 in HF patients was 5.73±10.32pg/ml, significantly higher(P<0.01) than that of the control(1.55±0.23 pg/ml). The level of IL-13 was 17.69±10.09 pg/ml, significantly higher(P<0.05) than that of the control (11.05±9.65 pg/ml). The levels of IFN-γand TNF-αin HF patients were 24.09±40.05 pg/ml and 4.76±4.41pg/ml, respectively, significantly higher(P<0.01) than that in control group (1.72±0.46 pg/ml and 1.52±1.15 pg/ml). There was a significant difference between mild(2.71±2.65 pg/ml) and severe ( 9.80±14.68 pg/ml) HF patients in level of IL-10(P<0.05). The level of IL-13 in severe HF patients was 23.52±11.87 pg/ml, significantly higher(P<0.01) than that in mild HF patients (13.35±5.51 pg/ml). Also a significant difference(P<0.05)was found in level of IFN-γin both severe(12.90±16.08 pg/ml )and mild (32.42±49.71 pg/ml)HF subjects. Our observation did not reveal any obvious difference of TNF-αin severe( 5.08±4.85 pg/ml) and mild (4.53±4.10 pg/ml)groups. A statstically significant difference of IL-13 was noted in mild and severe HF patients. The level of IL-10 in female below 60 years of age with mild HF was 3.13±3.15 pg/ml , significantly higher(P<0.05) than that in male (1.74±0.36 pg/ml). No sexual difference was seen in the cytokinses tested above in severe HF. The levels of HA and LN in severe HF patients were 273.42±216.54ng/ml and 152.48±43.32 ng/ml respectively, significantly higher(P<0.01) than HA (48.88±30.96 ng/ml)and LN (125.05±19.72 ng/ml) in mild HF. The present study did not show a difference between HA and LN in mild HF patients and in normal persons. There is a possitive correlation between IL-10 and IL-13 (r=0.375, P<0.01). A close correlation between IL-10, IL-13, and HA was noted (P<0.01); HA increased with LN (r=0.325,P<0.01). Conclusion: The level of cytokines in HF caused by S. japonicum varies in severity. The results of the present investigation showed that a high level production of IL-13 was associated with severe HF. Furthermore, our data show that TNF-αis not closely associated with the degree of HF, supporting the hypothesis of a fibrogenesis pathway that is dependent on IL-13 but not on TNF-α. A high level of IFN-γmay plays a protective role in HF of schistosomiasis. High level of IL-10 in severe HF patients caused by S. japonicum need to be further observed. Factors of the ages of patients and severity of HF in schistosomiasis did not differ in schistosome infection and underlined HBV. Our results indicate that HA seems more sensitive than LN as a marker for differiential diagnosis of early and advanced hepatic fibrosis caused by schistosomiasis. |
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