Slow resolution of inflammation in severe adult dengue patients.
The pathogenesis of severe dengue has not been fully elucidated. The inflammatory response plays a critical role in the outcome of dengue disease.



In this study, we investigated the levels of 17 important inflammation mediators in plasma collected from mild or severe adult dengue patients at different time points to understand the contribution of inflammation to disease severity and to seek experimental evidence to optimize the existing clinical treatment strategies. Patients were simply classified as mild and severe dengue according to the 2009 WHO classification. Plasma was collected on day 3-5, 6-7, 8-10 and 14-17 of illness. Levels of 17 inflammation mediators including TNF-α, IL-1α, IFN-γ, IL-6, IFN-α, MIF, IL-10, IL-1RA, IL-8, IP-10, MCP-1, RANTES, GRO, eotaxin-1, sICAM-1 and sVCAM-1 were determined by a multiplex Luminex® system. Different trends of inflammation mediators throughout the disease were compared between mild and severe patients.



Inflammation mediators including IL-1α, IFN-γ, IL-10, IL-8, IP-10, MCP-1 and sVCAM-1 displayed significant differences on day 8-10 of illness between mild and severe dengue patients. Their concentrations were higher in severe patients than mild ones at the same time points. Moreover, those cytokines decreased gradually in mild patients but not in severe patients.



Our results revealed the coexistence of excessive inflammatory response and slow resolution of inflammation in severe adult dengue patients. Hence suppression and/or pro-resolution of inflammation could be a potential therapeutic approach for treatment of severe dengue.
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China.
Lingzhai
L
Zhao
Department of Immunobiology, Jinan University, Guangzhou, Guangdong, 510632, China.
Xiuyan
X
Huang
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China.
Wenxin
W
Hong
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China.
Shuang
S
Qiu
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China.
Jian
J
Wang
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China.
Lei
L
Yu
Department of Immunobiology, Jinan University, Guangzhou, Guangdong, 510632, China. zengyaoying@gmail.com.
Yaoying
Y
Zeng
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China. gz8htxh@126.com.
Xinghua
X
Tan
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510060, China. gz8hzfc@126.com.
Fuchun
F
Zhang
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D054413:Chemokine CCL11 / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology; D018946:Chemokine CCL5 / Q000276:immunology; D054360:Chemokine CXCL1 / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation; D018836:Inflammation Mediators; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053582:Interleukin-1alpha / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019595:Severe Dengue / Q000276:immunology*; D012720:Severity of Illness Index; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology; D055815:Young Adult
C515456:CCL11 protein, human; C111835:CCL2 protein, human; C483024:CCL5 protein, human; C475829:CXCL1 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D016207:Cytokines; C508609:IL10 protein, human; C508584:IL1A protein, human; C507763:IL1RN protein, human; D018836:Inflammation Mediators; D016898:Interferon-alpha; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D015850:Interleukin-6; D016209:Interleukin-8; D008263:Macrophage Migration-Inhibitory Factors; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
Adhesion molecule; Chemokine; Cytokine; Resolution of inflammation; Severe dengue