title: Leukotrienes are upregulated and associated with human T-lymphotropic virus type 1 (HTLV-1)-associated neuroinflammatory disease.
abstract: Leukotrienes (LTs) are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1) infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Bioactive LTB(4) and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4) and LTC(4) positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+) and CD8(+) T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.
authors.affiliation: Laboratório de Inflamação e Imunologia das Parasitoses, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil.
authors.forename: Bruno Caetano
authors.initials: BC
authors.lastname: Trindade
authors.forename: Carlos Artério
authors.initials: CA
authors.lastname: Sorgi
authors.forename: Larissa Deadame de Figueiredo
authors.initials: LD
authors.lastname: Nicolete
authors.forename: Tathiane Maistro
authors.initials: TM
authors.lastname: Malta
authors.forename: Mariana Tomazini
authors.initials: MT
authors.lastname: Pinto
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins Filho
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015289:Leukotrienes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D011533:Proviruses / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018077:Receptors, Leukotriene / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D018925:Chemokines; D015289:Leukotrienes; D012333:RNA, Messenger; D018077:Receptors, Leukotriene