Circulating levels of the neuropeptide hormone somatostatin may determine hepatic fibrosis in Schistosoma mansoni infections

Abstract

The neuropeptide hormone somatostatin reduces fibrosis and Schistosoma-caused clinical morbidity in the rodent model. In our study we aimed to delineate an association between fibrosis and the inability to generate critical levels of endogenous somatostatin in S. mansoni infected subjects. In June 2001, 85 subjects from the district dispensary at Richard Toll in the Medical Region of Saint-Louis, Senegal, were selected. Fifty-seven subjects were infected with S. mansoni of whom 32 were suffering from severe morbidity (SM). Twenty-eight subjects showed an inactive disease status with no evident infection at the actual time of study. All subjects were classified according to age, sex, occupation, height, weight, and parasite eggs per gram. All 85 participated in a water contact and morbidity questionnaire, underwent a clinical examination and donated 5ml of peripheral blood for detecting plasma levels of somatostatin. Ultrasonography detected fibrosis grade in all the subjects. To address whether inherent somatostatin levels determined clinically evident disease severity (epg, hepatomegaly, splenomegaly, hematemesis, ascites), the mean somatostatin values of the inactive disease status group and severe morbidity group were compared. Low somatostatin levels were depicted in subjects with severe morbidity symptoms associated with schistosomiasis as compared to exposed but inactive disease status subjects residing in the same region. Logistic regression analysis indicated that with decreasing somatostatin values the probability of severe morbidity increased with age being a confounding factor. To address whether inherent somatostatin levels determined fibrosis and if this association was significant, plasma somatostatin levels of non-fibrotics (ultrasonographic grading A), and fibrotics (ultrasonographic grading B-E) were compared. In all age groups as well as in adults alone, mean somatostatin levels were higher in the non-fibrotic group as compared to the fibrotics group, the difference being significant. The group B comprised of borderline fibrotic cases, therefore a separate analysis was done between groups A (non-fibrotics) and groups C, D (confirmed fibrotics). Mean somatostatin values were higher in the non-fibrotic group as compared to the fibrotics group, the difference being borderline significant. In schistosomiasis patients, circulating levels of somatostatin by binding to hepatic stellate cells (HSC) may modulate fibrosis. This phenomenon is regulated by age whereas gender and prior treatment have no effect on this association. Host specific somatostatin levels may create a 'preset environment' status that can determine progression to severe fibrosis.