TY - JOUR
T1 - Thrombocytopenia May Mediate Disease Severity in Plasmodium Falciparum Malaria Through Reduced Transforming Growth Factor Beta-1 Regulation of Pro- and Anti-Inflammatory Cytokines
AU - Hanisch, Benjamin R.
AU - Bangirana, Paul
AU - Opoka, Robert
AU - Park, Gregory S.
AU - John, Chandy C.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Background Transforming growth factor beta-1 (TGF-β1) is an important regulator of inflammation. Platelets are a major source of TGF-β1, and are reduced in severe malaria. However, the relationships between TGF-β1 concentrations and platelet counts, pro- and anti-inflammatory cytokine and chemokine concentrations, and disease severity in malaria have not been characterized. Methods Platelet counts and serum concentrations of TGF-β1 and interleukin-1beta (IL–1β), IL-6, IL-10, interferon (IFN)–γ, tumor necrosis factor (TNF)- α and RANTES were measured at the time of presentation in Ugandan children with cerebral malaria (CM, n=75), uncomplicated malaria (UM, n=67) and healthy community children (CC, n=62). Results TGF-β1 concentrations decreased with increasing severity of disease (median concentrations (25th, 75th percentile) in ng/ml in CC, 41.4 (31.6, 57.4), UM, 22.7 (14.1, 36.4), CM, 11.8 (8, 21), P for trendPP=0.0015). In children with CM, TGF-β1 concentration correlated negatively with IFN-γ, IL-6, and IL-10 and positively with RANTES concentrations (all PConclusions TGF-β1 concentrations decrease with increasing P. falciparum disease severity. In cerebral malaria, thrombocytopenia correlates with decreased TGF-β1, and decreased TGF-β1 correlates with cytokine/chemokine changes associated with increased disease severity and death. Thrombocytopenia may mediate disease severity in malaria through reduced TGF-β1-mediated regulation of cytokines associated with severe disease.
AB - Background Transforming growth factor beta-1 (TGF-β1) is an important regulator of inflammation. Platelets are a major source of TGF-β1, and are reduced in severe malaria. However, the relationships between TGF-β1 concentrations and platelet counts, pro- and anti-inflammatory cytokine and chemokine concentrations, and disease severity in malaria have not been characterized. Methods Platelet counts and serum concentrations of TGF-β1 and interleukin-1beta (IL–1β), IL-6, IL-10, interferon (IFN)–γ, tumor necrosis factor (TNF)- α and RANTES were measured at the time of presentation in Ugandan children with cerebral malaria (CM, n=75), uncomplicated malaria (UM, n=67) and healthy community children (CC, n=62). Results TGF-β1 concentrations decreased with increasing severity of disease (median concentrations (25th, 75th percentile) in ng/ml in CC, 41.4 (31.6, 57.4), UM, 22.7 (14.1, 36.4), CM, 11.8 (8, 21), P for trendPP=0.0015). In children with CM, TGF-β1 concentration correlated negatively with IFN-γ, IL-6, and IL-10 and positively with RANTES concentrations (all PConclusions TGF-β1 concentrations decrease with increasing P. falciparum disease severity. In cerebral malaria, thrombocytopenia correlates with decreased TGF-β1, and decreased TGF-β1 correlates with cytokine/chemokine changes associated with increased disease severity and death. Thrombocytopenia may mediate disease severity in malaria through reduced TGF-β1-mediated regulation of cytokines associated with severe disease.
U2 - 10.1097/INF.0000000000000729
DO - 10.1097/INF.0000000000000729
M3 - Article
JO - Paediatrics and Child Health, East Africa
JF - Paediatrics and Child Health, East Africa
ER -
