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Increased ratio of tumor necrosis factor-alpha to interleukin-10 production is associated with Schistosoma haematobium-induced urinary-tract morbidity.

Wamachi AN, Mayadev JS, Mungai PL, Magak PL, Ouma JH, Magambo JK, Muchiri EM, Koech DK, King CH, King CL

Kenya Medical Research Institute, Nairobi, Kenya.

Bladder and kidney disease, which affect approximately 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.

Published 5 November 2004 in J Infect Dis, 190(11): 2020-30.
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