title: Increased ratio of tumor necrosis factor-alpha to interleukin-10 production is associated with Schistosoma haematobium-induced urinary-tract morbidity.
abstract: 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.
authors.affiliation: Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Alex N
authors.initials: AN
authors.lastname: Wamachi
authors.forename: Jyoti S
authors.initials: JS
authors.lastname: Mayadev
authors.forename: Peter L
authors.initials: PL
authors.lastname: Mungai
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Magak
authors.forename: John H
authors.initials: JH
authors.lastname: Ouma
authors.forename: Japhet K
authors.initials: JK
authors.lastname: Magambo
authors.forename: Eric M
authors.initials: EM
authors.lastname: Muchiri
authors.forename: Davy K
authors.initials: DK
authors.lastname: Koech
authors.forename: Charles H
authors.initials: CH
authors.lastname: King
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
mesh_terms: D000293:Adolescent; D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007630:Kenya; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D010270:Parasite Egg Count; D015995:Prevalence; D012307:Risk Factors; D012424:Rural Population; D012548:Schistosoma haematobium / Q000276:immunology* / Q000302:isolation & purification; D012553:Schistosomiasis haematobia / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014463:Ultrasonography; D001743:Urinary Bladder / Q000000981:diagnostic imaging
chemical_list: D000947:Antigens, Helminth; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10