Increased Ratio of Tumor Necrosis Factor–α to Interleukin‐10 Production Is Associated with Schistosoma haematobium–Induced Urinary‐Tract Morbidity
1Kenya Medical Research Institute, 2Jomo Kenyatta University of Agriculture and Technology, and 3Division of Vector Borne Diseases, Nairobi, Kenya; 4Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio
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 (
) had dysregulated cytokine production leading to enhanced granulomatous responses, compared with subjects of similar age and intensity of infection without morbidity (
). Peripheral blood mononuclear cells from subjects with morbidity produced 8‐fold greater levels of egg antigen–driven tumor necrosis factor (TNF)–α and had a 99‐fold greater mean TNF‐α: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‐α production in response to endotoxin, suggesting an innate hyperresponsiveness. These results indicate that increased TNF‐α production, relative to that of IL‐10, is associated with developing bladder‐wall morbidity with S. haematobium infection.
Received 2 July 2003; accepted 18 June 2004; electronically published 27 October 2004.
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Presented in part: 12th National Institutes of Allergy and Infectious Diseases International Centers for Tropical Disease Research, Bethesda, MD, 13–15 May 2003.
Financial support: National Institute of Allergy and Infections Disease (grant AI45473); National Institutes of Health (Fogarty Training Grant).