Role of Steroids in Modulating Levels of Cytokines in Patients of Dengue Fever and Warning Signs

Abstract

Dengue fever (DF), also known as break-bone fever, is a tropical infectious disease caused by the dengue virus. Dengue virus is a member of Flaviviridae family in the genus Flavivirus [1,2]. The dengue virus complex comprises of four antigenic ally related viruses designated dengue virus serotypes 1 through 4. Although DF is a self-limited febrile illness, it can progress to dengue hemorrhagic fever (DHF) in a number of patients. DHF is characterized by thrombocytopenia and increased vascular permeability leading to prominent hemorrhagic manifestations and a increased mortality [3]. Analysis of serum from patients infected with dengue virus indicates that concentrations of IL10 [4], TNF-α [5], IL-8 [6], IL-12 [7], IFN-Υ [8], IFN-α [9]. And soluble TNF and IL-2 receptors are increased during DF and DHF. Cell cultures infected with the dengue virus release increased concentrations of inflammatory cytokines and other mediators. Prior studies have also correlated increased levels of several cytokines with disease severity and may have prognostic value [10-15]. In addition, these studies show that levels of cytokines adversely affecting the coagulation cascade tend to be higher in DHF versus DF [10, 16]. Given the critical role of cytokines in the inflammatory process and Coagulopathy, there have been numerous attempts to suppress their levels in an attempt to control various diseases [17-19]. Glucocorticoids have an inhibitory effect on a broad range of immune responses mediated by T cells and B cells, as well as potent suppressive effect on the effector functions of phagocytes. They inhibit the synthesis of almost all known cytokines (IL 1, 2, 3, 4, 5, 6, 8, 10, 13, GMCSF, TNF-α and IFN-Υ). Since inflammatory cytokines have been proposed to play an important role in pathogenesis of dengue fever and its various complications there has been considerable interest in studying the potential role of corticosteroids as a potential therapy for DF and DHF. We conducted a study to see the effect of corticosteroids on the levels of cytokines in dengue patients and hence provide an immuno pathological basis for the use of corticosteroids in DF, a highly debated practice with many studies giving conflicting results.