Elevated plasma interleukin-10 levels in acute dengue correlate with disease severity

Green, Sharone; Vaughn, David W.; Kalayanarooj, Siripen; Nimmannitya, Suchitra; Suntayakorn, Saroj; Nisalak, Ananda; Rothman, Alan L.; Ennis, Francis A.

doi:10.1002/(sici)1096-9071(199911)59:3<329::aid-jmv12>3.0.co;2-g

Cited by 173 publications

(112 citation statements)

References 34 publications

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“…This association remained significant after excluding the one subject who was studied after a primary DV infection and who showed no peptide-specific T cell response. Previous studies had demonstrated that DHF was associated with greater activation of CD8 ϩ T cell responses in general (11,12,43,44) but had not shown the association with T cell responses directed at DV epitopes. Because we focused on the response to a single T cell epitope, we cannot say with certainty whether the overall frequency of DV-reactive T cells is higher in subjects with DHF than those with DF.…”

Section: Discussionmentioning

confidence: 91%

T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity

Zivna

Green

Vaughn

et al. 2002

The Journal of Immunology

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128

117

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Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221–232 of the DV NS3 protein, in 10 HLA-B*07+ Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF than in those who had experienced DF. We also detected peptide-specific T cells in PBMC obtained at the time of the acute DV infection in 2 of 5 subjects. These data suggest that the NS3 (221–232) epitope is an important target of CD8+ T cells in secondary DV infection and that the activation and expansion of DV-specific T cells is greater in subjects with DHF than in those with dengue fever. These findings support the hypothesis that activation of DV-specific CD8+ T cells plays an important role in the pathogenesis of DHF.

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Section: Discussionmentioning

confidence: 91%

T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity

Zivna

Green

Vaughn

et al. 2002

The Journal of Immunology

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128

117

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“…Culture fluids from dengue virus-infected peripheral blood monocytes activated endothelial cells, as measured by upregulation of cell adhesion molecules (Anderson et al, 1997), and increased the permeability of endothelial cells in vitro (Carr et al, 2003). It has also been reported that cytokines play an important role in the pathogenesis of DHF , and plasma leakage in DHF patients is associated with the elevation of plasma levels of various cytokines (Green et al, 1999;Kurane et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood mononuclear cells increase the permeability of dengue virus-infected endothelial cells in association with downregulation of vascular endothelial cadherin

Dewi

Takasaki

Kurane

2008

Journal of General Virology

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Plasma leakage is one of the characteristic features of dengue haemorrhagic fever. The interaction among peripheral blood mononuclear cells (PBMCs), dengue virus and endothelial cells was analysed in vitro. Human umbilical vein endothelial cells (HUVECs) were infected with dengue-2 virus (DV-2) at an m.o.i. of 0.5 p.f.u. per cell. PBMCs were added to DV-2-infected HUVECs, and transendothelial electrical resistance (TEER) and transalbumin permeability were assessed. Dengue virus infection at an m.o.i. of 0.5 p.f.u. per cell alone did not decrease the TEER, but addition of PBMCs decreased the TEER, increased the albumin permeability and induced morphological changes of HUVECs. The extent of the decrease was more profound with adherent PBMCs than with non-adherent PBMCs. The expression of vascular endothelial cadherin (VE-cadherin) was examined using real-time RT-PCR and immunofluorescence. Addition of PBMCs to DV-2-infected HUVECs decreased the levels of mRNA transcripts and cell-surface expression of VE-cadherin. The results indicate that PBMCs increased the permeability of DV-2-infected HUVECs and that the increased permeability was concomitant with morphological change and the decrease in VE-cadherin expression. The results suggest that functional impairment of the DV-2-infected HUVEC monolayer was caused by interaction with PBMCs.

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“…The interaction of IL-33 with ST2L leads to the induction of the Th2 cytokines IL-4, IL-5 and IL-13 through a signaling mechanism that involves the activation of NF-κB and MAP kinases [51]. In dengue virus infections a shift from a predominant Th1 response to a Th2 response around the time of defervescence appears to correlate with disease severity [14,53] and higher levels of IL-10 and IL-13 have been found in DHF compared to DF patients [13,14,54]. Therefore, elevated levels of sST2 protein could be part of a downregulation mechanism triggered to attenuate the Th2 response that occurs in dengue patients.…”

Section: Discussionmentioning

confidence: 99%

“…Cross reactivity also generates a dysfunctional T cell response that results in suboptimal clearance of the virus and an uncontrolled production of soluble mediators [9]. Elevated circulating levels of both type 1 (Th1) and type 2 (Th2) cytokines and various chemokines including gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1β), IL-6, IL-10, IL-13, IL-8, macrophage chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 1 beta (MIP-1β) have been detected in dengue infected patients [10][11][12][13][14][15][16][17][18], and the kinetics and persistence of some of these mediators seem to be related to the severity of the disease.…”

Section: Introductionmentioning

confidence: 99%

Elevated levels of soluble ST2 protein in dengue virus infected patients

et al. 2008

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Levels of the soluble form of the interleukin-1 receptor like 1 protein (IL-1RL-1 / ST2) are elevated in the serum of patients with diseases characterized by an inflammatory response. The objective of this study was to determine the concentration of soluble ST2 (sST2) in dengue infected patients during the course of the disease. Twenty four patients with confirmed dengue infection, classified as dengue fever, and eleven patients with other febrile illness (OFI) were evaluated. Levels of sST2 in serum and laboratory variables usually altered during dengue infections were measured. Dengue infected patients had higher serum sST2 levels than OFI at the end of the febrile stage and at defervescence (p=0.0088 and p=0.0004 respectively). Patients with secondary dengue infections had higher serum sST2 levels compared with patients with primary dengue infections (p=0.047 at last day of fever and p=0.030 at defervescence). Furthermore, in dengue infected patients, we found a significant negative correlation of sST2 with platelet and WBC counts, and positive correlation with thrombin time and transaminases activity. We suggest that sST2 could be a potential marker of dengue infection, could be associated with severity or could play a role in the immune response in secondary dengue virus infection.

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Elevated plasma interleukin-10 levels in acute dengue correlate with disease severity

Cited by 173 publications

References 34 publications

T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity

T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity

Peripheral blood mononuclear cells increase the permeability of dengue virus-infected endothelial cells in association with downregulation of vascular endothelial cadherin

Elevated levels of soluble ST2 protein in dengue virus infected patients

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