Role of cytokines secreted from mast cells act on dengue hemorrhagic fever pathogenesis

Abstract

Dengue infection is currently a major human health problem across the globe, especially in Thailand. The lack of an effective treatment or vaccine makes research into the pathogenesis and the development of promising important treatments. This study aimed to investigate the quantity and type of cytokines that are secreted from mast cells after dengue infection related to the pathogenesis of human vascular endothelial cells (HUVEC). The study analyzed the quantity of cytokine secretion from human mast cells (HMC-1) compared with monocytic cells (THP-1), after infection with type 2-dengue virus (DENV-2-16681) by high throughput magnetic bead-based Bio-PlexÒassay. The effect of cytokine stimulation from HMC-1 and THP-1 on the HUVEC was determined. The results showed significantly increased levels of cytokines, which were similar to those secreted from Th1 and Th2 including interleukin (IL)-5, IL-8, tumor necrosis factor (TNF)-a, macrophage inflammatory protein (MIP)-1, and granulocyte macrophage colony-stimulating factor (GM-CSF) (p<0.01). However, the study found that there was specificity between cytokine secretions and particular cell types. It was found that TNF-a secretion was higher in THP-1 cells, while IL-5 was found at higher levels in HMC-1 cells after dengue infection. The stimulation of dengue-infected HMC-1 cells on vascular endothelial cells showed a higher secretion of ICAM-1 and VCAM-1 in THP-1 cells. This study concluded that increased secretion of IL-5 from mast cells has an effect on vascular endothelial cells, which is an important step to explain the pathogenesis of dengue. This work may elucidate the role of mast cells in dengue pathogenesis to determine disease severity and development of novel treatments.