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, but Low Levels of IL-5, Are Associated with Hepatosplenic Disease in Human Schistosomiasis Mansoni1
*
Kenya Medical Research Institute,
Division of Vector Borne Diseases, Kenyan Ministry of Health, and
Department of Human Pathology, University of Nairobi, Nairobi, Kenya; and
§
Department of Pathology, Cambridge University, Cambridge, United Kingdom
In a case-control study based in two areas of Kenya, hepatosplenic
schistosomiasis mansoni was shown to be linked with low levels of IL-5
and with correspondingly high IFN-
, TNF, and circulating soluble TNF
receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the
hepatosplenic cases responded to in vitro Ag stimulation with
significantly higher levels of IFN- and TNF, but lower levels of
IL-5, compared with nonhepatosplenic controls matched for age and
infection intensity. Most of these correlations were confounded by
differences between geographical areas. However, principle component
analysis identified a high IFN- and TNF, and low IL-5 axis in the
data as the first principle component; this was significantly
associated with hepatosplenomegaly (p <
0.0005) even after controlling for area. High plasma levels of sTNFR-I
(p < 0.001), sTNFR-II,
(p < 0.0001), and sICAM-1
(p < 0.009) were also significantly
associated with hepatosplenomegaly, independently of area, in the case
of the soluble forms of both TNF receptors. These parameters were
negatively related to IL-5. These results suggest that proinflammatory
cytokines are involved in the hepatosplenic disease process in infected
individuals who have low anti-inflammatory Th2 responses and that
sTNFR may be a useful circulating marker for this disease process,
perhaps reflecting the level of TNF activity in hepatic tissues.
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