title: Cellular and cytokine correlates of severe dengue infection.
abstract: BACKGROUND
  The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF.
  
  
  RESULTS
  By using ex vivo IFNγ ELISpot assays we determined DENV-NS3 specific responses in patients with varying severity of DHF. Other cytokines produced by DENV-NS3 specific T cells were determined by using multiple bead array analysis (MBAA). We also determined the serum cytokine levels using MBAA, lymphocyte subsets and Annexin V expression of lymphocytes in patients with varying severity of DHF. Of the 112 DHF patients studied, 29 developed shock. Serum IL-10 and IP-10 levels positively and significantly correlated with T cell apoptosis while IL-10 levels inversely correlated with T cell numbers. In contrast, TGFß showed a very significant (P<0.0001) and positive correlation (Spearman's R = 0.65) with the platelet counts, consistent with platelet release. We found that whilst patients with severe dengue had lower total T cell numbers, the DV-NS3 specific T cells persisted and produced high levels of IFNγ but not TNFα, IL-3, IL-13, IL-2, IL-10 or IL-17.
  
  
  CONCLUSIONS
  Our data suggest that serum IL-10, TNFα and TGFβ differentially associate with dengue disease severity.
authors.affiliation: Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayawardanapura, Nugegoda, Sri Lanka.
authors.forename: Gathsaurie Neelika
authors.initials: GN
authors.lastname: Malavige
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Huang
authors.forename: Maryam
authors.initials: M
authors.lastname: Salimi
authors.forename: Laksiri
authors.initials: L
authors.lastname: Gomes
authors.forename: S D
authors.initials: SD
authors.lastname: Jayaratne
authors.forename: Graham S
authors.initials: GS
authors.lastname: Ogg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018925:Chemokines / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D003715:Dengue / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D011419:Propidium / Q000494:pharmacology; D013601:T-Lymphocytes / Q000821:virology; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018925:Chemokines; D016207:Cytokines; D010455:Peptides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011419:Propidium