The Relationship of Endotoxaemia to Peripheral and Central Nervous System Inflammatory Responses in Human African Trypanosomiasis

Lorna MacLean, Eltayb A Aboubaker, Peter G E Kennedy, Jeremy M Sternberg

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Abstract

Endotoxaemia has been described in cases of Human African trypanosomiasis (HAT), but it is unclear if this phenomenon influences inflammatory pathology either in the periphery or central nervous system (CNS). We studied endotoxin concentrations in the plasma and cerebrospinal fluid (CSF) of Trypanosoma brucei rhodesiense patients using the chromogenic Limulus Amoebocyte lysate assay. The relationship of endotoxin concentration to the presentation of gross signs of inflammation and the inflammatory/counter-inflammatory cytokine profile of the relevant compartments were analysed. We demonstrate that HAT patients exhibit parasitaemia-independent plasma endotoxaemia, and that this is associated with splenomegaly and lymphadenopathy. Endotoxin concentrations normalize rapidly after treatment. There was no evidence of endotoxin release in the CNS. A rapid normalization of endotoxin levels after treatment and lack of association with parasitaemia suggest that gut leakage is the main source of endotoxin in the circulation. Low CSF endotoxin concentrations and a lack of any association with neuroinflammatory markers or neurological sequelae suggest that endotoxin does not play a role in the pathogenesis of the disease in the CNS.
Original languageEnglish
Pages (from-to)557-562
Number of pages6
JournalParasitology
Volume144
Issue number4
Early online date29 Nov 2016
DOIs
Publication statusPublished - 1 Apr 2017

Bibliographical note

This work was funded the Wellcome Trust (grant no. 082786 to J. M. S.)

Keywords

  • Human African trypanosomiasis
  • Trypanosoma brucei rhodesiense
  • Endotoxaemia
  • inflammatory response
  • cerebrospinal fluid

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