Increased Ratio of Tumor Necrosis Factor- alpha to Interleukin-10 Production Is Associated with Schistosoma haematobium-Induced Urinary-Tract Morbidity.

摘要

Bladder and kidney disease, which affect ~25%-30% of subjects infected with Schistosoma haematobium, are mediated by T cell-dependent granulomatous responses to schistosome eggs. To determine why only some infected subjects develop disease, we examined the hypothesis that infected Kenyan subjects with ultrasound-detected urinary-tract morbidity (n=49) had dysregulated cytokine production leading to enhanced granulomatous responses, compared with subjects of similar age and intensity of infection without morbidity (n=100). Peripheral blood mononuclear cells from subjects with morbidity produced 8-fold greater levels of egg antigen-driven tumor necrosis factor (TNF)- alpha and had a 99-fold greater mean TNF- alpha : interleukin (IL)-10 ratio, compared with subjects without disease. No differences in cytokine response to non-egg-derived schistosome antigens were observed between groups. Subjects with morbidity had increased TNF- alpha production in response to endotoxin, suggesting an innate hyperresponsiveness. These results indicate that increased TNF- alpha production, relative to that of IL-10, is associated with developing bladder-wall morbidity with S. haematobium infection.