Secretory phospholipase A2 in the pathogenesis of acute dengue infection:

Abstract

Introduction: Platelet activating factor (PAF) is an important mediator of vascular leak in acute dengue. Phospholipase A2s (PLA2) are inflammatory lipid enzymes that generate and regulate PAF and other mediators associated with mast cells. We sought to investigate if mast cell activation and increases in secretory sPLA2s are associated with an increase in PAF and occurrence of dengue haemorrhagic fever (DHF). Methods: The changes in the levels of mast cell tryptase, PAF and the activity of sPLA2 were determined throughout the course of illness in 13 adult patients with DHF, and 30 patients with dengue fever (DF). Results: We found that sPLA2 activity was significantly higher in patients with DHF when compared to those with DF, during the first 120 h of clinical illness. sPLA2 activity was significantly associated with PAF levels, which were also significantly higher in patients with DHF. Although levels of mast cell tryptase were higher in patients with DHF, the difference was not significant, and the levels were not above the reference ranges. sPLA2 activity significantly correlated with the degree of viraemia in patients with DHF but not in those with DF. Conclusion: sPLA2 appears to play an important role in the pathogenesis of dengue. Since its activity is significantly increased during the early phase of infection in patients with DHF, this suggests that understanding the underlying mechanisms may provide opportunities for early intervention. Secretory phospholipase A2 (sPLA2) activity was significantly increased in patients with dengue haemorrhagic fever, compared to those with dengue fever, during the first 120 h of clinical illness. sPLA2 activity was significantly associated with levels of platelet activating factor, which was found to associate with vascular leak. Since the sPLA2 activity is significantly increased during the early phase of infection in patients with DHF, this suggests that events that occur early in the course of infection are important determinants of subsequent disease severity.