Cytokine Biomarkers and Their Potential Indications in Dengue Diseases

As dengue infection is one of the most arboviral infections worldwide without available vaccines and medicine, severe dengue is highly dependent on timely and proper medical treatment. However, there is no reliable severity prediction marker for dengue infection progression as dengue warning signs from WHO 2009 still have high sensitivity but low specificity. The other proposed markers are also not readily accessible in clinical settings, especially in rural areas. We developed a 24-cytokine panel from the literature study to overcome this problem and then used it in the dengue patient plasma using the Multiplex Cytokine Assay. Further, Assay results were analyzed, and promising severity biomarkers were proposed. The 24-cytokine panel (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CXCL-10, IL-4, CCL-2, CCL-4, CCL-5, IFN-α, GM-CSF, VEGF, IL-15, IL-13, IL-1Rα, IL-18, IL-12, CXCL-9, CCL-3, IL-17, IL-7, IL-1β, and IL-2) were the chemokine/cytokines that increased in the severe dengue infection. Our pilot study showed that only ten cytokines increased significantly in dengue to healthy (n = 30), with one decrease. However, in the severe to mild, only two cytokines increased statistically (IL-8 and IL-18). We expanded the sample number (n = 92) and found that some cytokines are upregulated (IL-18, IL-10, IL-6, and TNF⍺) and downregulated (IFN-γ, IFN-⍺, IL-7, IL-17, MCP-1, and RANTES) in the more severe dengue infection compared to its milder group. Further, we analyze the AUC of each variable and found that GPT, platelet, IL-6, IL-18, and RANTES are the best possible biomarkers for prediction in different severity groups. The result showed that our panel could be used to assess the severe condition, and GPT, platelet, IL-6, IL-18, and RANTES are promising biomarkers to predict dengue severity in various groups.