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

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.

• Authors: Benjamin R Hanisch, Paul Bangirana, Robert O Opoka, Gregory S Park, Chandy C John
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 34 Issue 7 Pg. 783-8 (Jul 2015) ISSN: 1532-0987 [Electronic] United States
• PMID: 25886788 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Transforming Growth Factor beta1

Topics

• Child
• Child, Preschool
• Cohort Studies
• Cytokines (blood)
• Female
• Humans
• Malaria, Cerebral (complications, pathology)
• Malaria, Falciparum (complications, pathology)
• Male
• Thrombocytopenia (pathology)
• Transforming Growth Factor beta1 (blood)
• Uganda