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

• Published in: The Journal of infectious diseases Vol. 190; no. 11; pp. 2020 - 2030
• Main Authors: Wamachi, Alex N., Mayadev, Jyoti S., Mungai, Peter L., Magak, Phillip L., Ouma, John H., Magambo, Japhet K., Muchiri, Eric M., Koech, Davy K., King, Charles H., King, Chistopher
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.12.2004; University of Chicago Press
• Subjects: Adolescent; Animals; Antigens; Antigens, Helminth - pharmacology; Bacteria; Biological and medical sciences; Cells, Cultured; Child; Child, Preschool; Cytokines; Female; Fundamental and applied biological sciences. Psychology; Granuloma; Humans; Infections; Infectious diseases; Interleukin-10 - biosynthesis; Kenya; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lipopolysaccharides; Male; Medical sciences; Microbiology; Morbidity; Parasite Egg Count; Parasitic diseases; Pathology; Prevalence; Risk Factors; Rural Population; Schistosoma haematobium; Schistosoma haematobium - immunology; Schistosoma haematobium - isolation & purification; Schistosomiasis; Schistosomiasis haematobia - diagnostic imaging; Schistosomiasis haematobia - epidemiology; Schistosomiasis haematobia - immunology; Tumor Necrosis Factor-alpha - biosynthesis; Ultrasonography; Urinary bladder; Urinary Bladder - diagnostic imaging; Urinary bladder diseases; Infection; Schistosoma haematobium; Microbiology; Cytokine; Interleukin 10; Helmintha; Plathelmintha; Invertebrata; Trematoda; Tumor necrosis factor α; Morbidity
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/425579

Bladder and kidney disease, which affect ∼25%–C30% 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 ultrasounddetected 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)-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-Cegg-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.