Thrombocytopenia may mediate disease severity in plasmodium falciparum malaria through reduced transforming growth factor beta-1 regulation of proinflammatory and anti-inflammatory cytokines

Benjamin R. Hanisch, Paul Bangirana, Robert O. Opoka, Gregory S. Park, Chandy John

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)783-788
Number of pages6
JournalPediatric Infectious Disease Journal
Volume34
Issue number7
DOIs
StatePublished - Jul 4 2015
Externally publishedYes

Fingerprint

Falciparum Malaria
Transforming Growth Factor beta
Thrombocytopenia
Anti-Inflammatory Agents
Cytokines
Malaria
Platelet Count
Chemokine CCL5
Chemokines
Interleukin-10
Interferons
Interleukin-6
Cerebral Malaria
Plasmodium falciparum
Interleukin-1beta
Nervous System
Blood Platelets
Tumor Necrosis Factor-alpha

Keywords

  • cerebral malaria
  • platelets
  • transforming growth factor beta

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Thrombocytopenia may mediate disease severity in plasmodium falciparum malaria through reduced transforming growth factor beta-1 regulation of proinflammatory and anti-inflammatory cytokines. / Hanisch, Benjamin R.; Bangirana, Paul; Opoka, Robert O.; Park, Gregory S.; John, Chandy.

In: Pediatric Infectious Disease Journal, Vol. 34, No. 7, 04.07.2015, p. 783-788.

Research output: Contribution to journalArticle

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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.",
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AU - Park, Gregory S.

AU - John, Chandy

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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, 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.

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