Proinflammatory Cytokines Are Modulated in Vietnamese Patients with Dengue Fever.

The clinical outcome of dengue is due to a complex interplay between dengue virus (DENV) and host immune factors, including complement and cytokine systems. Proinflammatory cytokines are mainly produced by monocytes in response to infectious pathogens. This study investigated the levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), and IL-12 in Vietnamese patients with dengue, and their correlations with the clinical outcome of dengue infection in 156 patients clinically classified as dengue without warning signs (DWS-, n = 87), dengue with warning signs (DWS+, n = 62), and severe dengue (SD, n = 7) patients as well as in 60 healthy controls (HCs). Serum TNF-α, IL-1ß, and IL-12 levels were quantified by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α, IL-1ß, and IL-12 levels were significantly increased in dengue patients compared with HCs (p < 0.0001). TNF-α levels were significantly correlated with white blood cells and platelet counts (rs = 0.52, 0.2; p < 0.0001, p = 0.018, respectively). IL-1ß levels were correlated with red blood cells counts and the levels of aspartate aminotransferase and alanine aminotransferase (rs = 0.23, 0.21, 0.23; p = 0.004, 0.012, 0.005, respectively). The results suggest that these three proinflammatory cytokines are associated with the clinical outcome of dengue and could play roles in the pathogenesis of the disease.

Combination of Vaccine Strain Measles Virus and Nimotuzumab in the Treatment of Laryngeal Cancer.

BACKGROUND/AIM: This study aims to investigate whether the combination of oncolytic viruses with chemoradiotherapy or other therapies is a promising strategy for cancer treatment. MATERIALS AND METHODS: The anticancer effects of measles virus (MeV) in combination with nimotuzumab in the treatment of laryngeal cancer were evaluated in vitro and in nude mice inoculated with Hep2 tumors. MTT assay and flow cytometry were used to examine cell death. RESULTS: Laryngeal cancer cells treated with MeV+nimotuzumab combination had a significantly lower survival rate compared to those treated with MeV or nimotuzumab alone (p<0.0001). In an animal model bearing human laryngeal tumor, the treated group had a higher survival rate (60%) compared to a untreated group (20%) (p<0.05), and the survival rate of the group treated with MeV+nimotuzumab combination was higher compared to the groups received single treatment. CONCLUSION: The MeV+nimotuzumab combination has greater anticancer activities in both laryngeal cancer cells and an animal model.

Regulation of p38MAPK-mediated dendritic cell functions by the deubiquitylase otubain 1.

Dendritic cells (DCs) are professional antigen presenting cells (APCs) that represent the essential link between innate and acquired immunity. Otubain (OTUB) 1 is shown to deubiquitinate TRAFs to suppress virus-induced inflammatory response. MAPK, a downstream molecule of TRAFs, is involved in regulating LPS-induced immune reactions and its activation is sensitive to the presence of OTUB1. Little is known about contributions of OTUB1 to changes in biological properties of DCs. The present study, therefore, explored whether DC functions are influenced by OTUB1. To this end, DCs were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs) and followed by treatment with lipopolysaccharide (LPS) in the presence or absence of OTUB1 siRNA. Expression of markers of cellular maturation and proliferation were analyzed by flow cytometry, and secretion of inflammatory cytokines and ability to stimulate CD4+ T-cells in allogenic mixed leukocyte reaction (allo-MLR) by ELISA, cell migration by a transwell migration assay and phagocytic capacity by FITC-dextran uptake measurement. As a result, treatment of the cells with OTUB1 siRNA prolonged activation of p38MAPK, increased CD54 expression and IL-6 release and reduced FITC-dextran uptake. Moreover, cytokine release produced from CD4+ T-cells in allo-MLR was different. The enhanced level of IFN-γ, but not other cytokine production was observed in the presence of siRNA OTUB1. All the effects were completely abolished when the cells were exposed with p38MAPK inhibitor SB203580. In conclusion, OTUB1 prevents the prolonged activation of p38MAPK, which in turn compromises DC functions.