title: Suppression of virus specific immune responses by IL-10 in acute dengue infection.
abstract: BACKGROUND
  Elevated IL-10 has been shown to be associated with severe dengue infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI.
  
  
  METHODS
  Ex vivo and cultured IFNγ ELISpot assays for dengue virus (DENV) NS3 protein and non dengue viral proteins were carried out in 26 patients with acute DI (16 with dengue haemorrhagic fever) and 12 healthy dengue seropositive individuals from Sri Lanka. DENV serotype specific (SS) responses were determined by using a panel of SS peptides.
  
  
  RESULTS
  Serum IL-10 level were significantly higher (p = 0.02) in those who did not have in vitro responses to DENV-SS peptides (mean 144.2 pg/ml) when compared to those who responded (mean 75.7 pg/ml). DENV-NS3 specific ex vivo IFNγ ELISpot responses were also significantly lower (p = 0.0001) in those who did not respond to DENV-SS peptides (mean 42 SFU/million PBMCs) when compared to those who responded to DENV-SS peptides (mean 1024 SFU/million PBMCs). Serum IL-10 levels correlated significantly (p = 0.03) and inversely (Spearmans R = -0.45) with ex vivo DENV-NS3 specific responses but not with ex vivo non DENV specific responses (Spearmans R = -014, p = 0.52). Blockage of IL-10 in vitro significantly increased (p = 0.04) the ex vivo IFNγ ELISpot DENV-NS3 specific responses but had no effect on responses to non DENV proteins.
  
  
  CONCLUSIONS
  IL-10 appears to contribute to the pathogenesis of acute dengue infections by inhibiting DENV-specific T cell responses, which can be restored by blocking IL-10.
authors.affiliation: Centre for Dengue Research, Faculty of Medical Sciences, University of Sri Jayawardanapura, Gangodawila, Nugegoda, Sri Lanka ; Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Gathsaurie Neelika
authors.initials: GN
authors.lastname: Malavige
authors.forename: Chandima
authors.initials: C
authors.lastname: Jeewandara
authors.forename: K M Luckmaal
authors.initials: KM
authors.lastname: Alles
authors.forename: Maryam
authors.initials: M
authors.lastname: Salimi
authors.forename: Laksiri
authors.initials: L
authors.lastname: Gomes
authors.forename: Achala
authors.initials: A
authors.lastname: Kamaladasa
authors.forename: S D
authors.initials: SD
authors.lastname: Jayaratne
authors.forename: Graham Stuart
authors.initials: GS
authors.lastname: Ogg
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003715:Dengue / Q000276:immunology* / Q000473:pathology*; D003716:Dengue Virus / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D013188:Sri Lanka; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma
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