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Pediatr Infect Dis J. 2015 Jul;34(7):783-8. doi: 10.1097/INF.0000000000000729.

Thrombocytopenia May Mediate Disease Severity in Plasmodium falciparum Malaria Through Reduced Transforming Growth Factor Beta-1 Regulation of Proinflammatory and Anti-inflammatory Cytokines.

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1
From the *Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; and †Department of Paediatrics, College of Health Sciences, Makerere University, Kampala, Uganda.

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, proinflammatory 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, 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 Plasmodium falciparum disease severity. In CM, 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.

PMID:
25886788
PMCID:
PMC4466060
DOI:
10.1097/INF.0000000000000729
[Indexed for MEDLINE]
Free PMC Article

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