Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-gamma, IL-4, IL-5 and IL-10 with age.
BACKGROUND
The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a Schistosoma haematobium endemic area and further investigated the relationship between the cytokine responses and infection intensity.


METHODS
Schistosome adult worm antigen-specific IFN-gamma, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to S. haematobium infection (aged 6 to 40 years old). The cytokines were measured using capture ELISAs and the data thus obtained together with S. haematobium egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches.


RESULTS
Age profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11-12 years) followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine) while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-gamma followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-gamma did not show a significant relationship with infection status or intensity and were positively associated with each other.


CONCLUSIONS
Taken together, these results show that the IL-10 responses develop early compared to the IL-5 response and may be down-modulating immunopathological responses that occur during the early phase of infection. The results further support current suggestions that the Th1/Th2 dichotomy does not sufficiently explain susceptibility or resistance to schistosome infection.
Institute of Immunology & Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, King's Buildings, West Mains Rd, Edinburgh, EH9 3JT, UK. f.mutapi@ed.ac.uk
Francisca
F
Mutapi
Georgina
G
Winborn
Nicholas
N
Midzi
Matthew
M
Taylor
Takafira
T
Mduluza
Rick M
RM
Maizels
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D010270:Parasite Egg Count; D012548:Schistosoma haematobium / Q000276:immunology*; D012553:Schistosomiasis haematobia / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D015030:Zimbabwe / Q000453:epidemiology
D016207:Cytokines; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma