title: The relationship of endotoxaemia to peripheral and central nervous system inflammatory responses in Human African Trypanosomiasis.
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.
authors.affiliation: Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery,James Black Centre,College of Life Sciences,University of Dundee,Dundee DD1 5EH,UK.
authors.forename: Lorna
authors.initials: L
authors.lastname: Maclean
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen,Zoology Building,Aberdeen AB24 2TZ,UK.
authors.forename: Eltayb A
authors.initials: EA
authors.lastname: Aboubaker
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow,Glasgow G61 1QH,UK.
authors.forename: Peter G E
authors.initials: PG
authors.lastname: Kennedy
authors.affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen,Zoology Building,Aberdeen AB24 2TZ,UK.
authors.forename: Jeremy M
authors.identifier: 0000-0002-1596-3622
authors.initials: JM
authors.lastname: Sternberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019446:Endotoxemia / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D014353:Trypanosomiasis, African / Q000097:blood* / Q000134:cerebrospinal fluid / Q000473:pathology*; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: 
                 Trypanosoma brucei rhodesiense
              ; Human African trypanosomiasis; cerebrospinal fluid; endotoxaemia; inflammatory response