Several studies have been performed to determine biomarkers that define the risk factors to developing severe forms of dengue. In this study, the levels of TNF-α, IL-6, IL-1, IL-17, soluble interleukin-1 receptor like 1 protein (sST2), soluble TNF-related apoptosis-inducing ligand (sTRAIL), IL-12 and soluble receptors for TNF (sTNF-RI and sTNF-RII) were determined by ELISA in dengue patients and monocyte/macrophage cultures. Dengue was classified as dengue without warning symptoms (DNWS), with warning symptoms (DWWS) and severe dengue (SD). High values of IL-6, sTNFRI, sTNFRII and sST2 were observed in DWWS and/or SD and IL-12 and sTRAIL in DNWS. TNF-α and IL-17 were increased not associated to the disease severity. High production of TNF-α, IL-1β, IL-12, IL-17, sST2 and sTRAIL and apoptosis expression were observed in dengue monocyte/macrophage cultures. This study shows that beneficial or deleterious biomarkers can be present in dengue regardless the disease severity and that monocytes may be in part the source of studied molecules.

This is the first study on the economic impact of dengue in the state of Zulia and in Venezuela. In spite of some limitations, results show that dengue is an important public health problem that causes great expense because of temporary absenteeism from work and that undermines regional and national economic development.

The purpose of this work was to determine the effect of melatonin on the nitric oxide levels in murine splenocytes cultured with the Venezuelan equine encephalomyelitis virus. After incubation, nitric oxide levels were measured by the diazotization assay. Those cultures with the Venezuelan equine encephalomyelitis virus increased nitric oxide levels. Splenocytes infected and treated with 100 and 150 microg/ml of melatonin, decreased significantly the nitric oxide levels when compared to infected and non-treated splenocytes. These findings show that splenocytes infected with the Venezuelan equine encephalomyelitis virus generate important amounts of nitric oxide and suggest that melatonin protects the mice infected with the Venezuelan equine encephalomyelitis virus by a mechanism involving the decreasing of nitric oxide concentrations in tissue.

The effect of melatonin (MLT) on the brain levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in Venezuelan equine encephalomyelitis (VEE) virus infection was determined. Brain homogenates from mice inoculated with 10 LD50 of VEE virus, untreated or treated with 500 microg MLT/kg body weight were assayed by ELISA to measure the levels of TNF-alpha and IL-1beta. MLT was injected daily starting 3 days before and continuing to 7 days after virus inoculation. Infected mice treated with MLT showed decreased levels of TNF-alpha when compared to the untreated infected mice on days 1, 3, 4, and 5 postinoculation (P < 0.001). In contrast, IL-1beta levels increased from days 1 to 5 in the infected mice treated with MLT when compared with the untreated infected animals (P < 0.01). The results suggest that the protective effect of MLT on the VEE virus infection could be due, among other factors, to a decrease in TNF-alpha synthesis along with an increase in the production of IL-1beta.

This study evaluated the levels of soluble interleukin-2 receptor (sIL-2R) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with dengue. Sera from 17 patients with dengue fever (DF), 15 with dengue hemorrhagic fever (DHF) and 12 healthy individuals were obtained. Increased levels of sIL-2R and sICAM-1 were found in patients with DF and DHF when compared to normal; those were not correlated with leukocytes, hepatic serum enzyme levels or haemostatic parameters. Levels of sIL-2R were related to the different grades of DHF. These results suggest that increased levels of sIL-2R and sICAM-1 are a common feature of dengue.