title: Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection.
abstract: BACKGROUND
  Leukotriene B4, a 5-lipoxygenase product of arachidonic acid with potent chemotactic effects on neutrophils, has not been assessed in dengue patients. In this study, plasma leukotriene B4 and serum high-sensitivity C-reactive protein levels were determined in adult patients during the febrile, convalescent and defervescent stages of dengue serotype-2 (DENV-2) infection, and compared with those of age-matched healthy and non-dengue febrile subjects. In vitro studies were performed to examine the effects of live and heat-inactivated DENV-2 on the activities and expression of 5-lipoxygenase in human neutrophils.
  
  
  RESULTS
  Plasma leukotriene B4 was elevated during the febrile stages of dengue infection compared to levels during convalescence and in study controls. Plasma leukotriene B4 also correlated with serum high-sensitivity C-reactive protein in dengue patients (febrile, r = 0.91, p < 0.001; defervescence, r = 0.87, p < 0.001; convalescence, r = 0.87, p < 0.001). Exposure of human neutrophils to DENV-2 resulted in a significant rise in leukotriene B4; the extent of increase, however, did not differ between exposure to live and heat-inactivated DENV-2. Pre-incubation of either live or heat-inactivated DENV-2 resulted in reduced leukotriene B4 release by neutrophils, indicating that contact with dengue antigens (and not replication) triggers the neutrophil response. Production of leukotriene B4 was associated with an increase in 5-lipoxygenase expression in human neutrophils; addition of MK886 (a 5-lipoxygenase activating protein inhibitor) attenuated further increase in leukotriene B4 production.
  
  
  CONCLUSIONS
  These findings provide important clinical and mechanistic data on the involvement of 5-lipoxygenase and its metabolites in dengue infection. Further studies are needed to elucidate the therapeutic implications of these findings.
authors.forename: Wai Mun
authors.initials: WM
authors.lastname: Loke
authors.forename: Angelia Yee
authors.initials: AY
authors.lastname: Chow
authors.forename: Karen
authors.initials: K
authors.lastname: Lam Mok Sing
authors.forename: Chung-Yung J
authors.initials: CY
authors.lastname: Lee
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
authors.forename: Erle C H
authors.initials: EC
authors.lastname: Lim
authors.forename: Amy M L
authors.initials: AM
authors.lastname: Quek
authors.forename: Eng Eong
authors.initials: EE
authors.lastname: Ooi
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E, NUHS Tower Block, Kent Ridge Road, Singapore. raymond_seet@nus.edu.sg.
authors.forename: Raymond C S
authors.initials: RC
authors.lastname: Seet
mesh_terms: D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002478:Cells, Cultured; D003715:Dengue / Q000145:classification / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000821:virology; D012703:Serotyping
chemical_list: D007975:Leukotriene B4; D002097:C-Reactive Protein; D001094:Arachidonate 5-Lipoxygenase