Thrombocytopenia May Mediate Disease Severity in Plasmodium Falciparum Malaria Through Reduced Transforming Growth Factor Beta-1 Regulation of Pro- and Anti-Inflammatory Cytokines
Document Type
Article
Department
Paediatrics and Child Health (East Africa)
Abstract
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 trend<0.0001). In children with CM or UM, TGF-β1 concentrations correlated positively with platelet count (CM, P<0.0001, UM, P=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 P<0.01). TGF-β1 concentration was not associated with death or adverse neurologic or cognitive outcomes in children with CM.
Conclusions
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.
Publication (Name of Journal)
The Pediatric infectious disease journal
DOI
10.1097/INF.0000000000000729
Recommended Citation
Hanisch, B. R.,
Bangirana, P.,
Opoka, R.,
Park, G. S.,
John, C. C.
(2015). Thrombocytopenia May Mediate Disease Severity in Plasmodium Falciparum Malaria Through Reduced Transforming Growth Factor Beta-1 Regulation of Pro- and Anti-Inflammatory Cytokines. The Pediatric infectious disease journal, 34(7), 783-783.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_paediatr_child_health/383
Comments
This work was published before the author joined Aga Khan University.