SHIFT FROM A TH1-TYPE RESPONSE TO TH2-TYPE IN DENGUE HAEMORRHAGIC FEVER

Dengue virus causes a mild febrile illness, dengue fever (DF) and at times a severe illness, dengue haemorrhagic fever (DHF), the pathogenesis of which is not fully known. The present study was undertaken to investigate the profile of Th1- and Th2-type cytokines in the sera of 117 patients of various grades of dengue illness and 21 normal healthy controls. Commercial sandwich ELISA kits were used to assay the serum levels of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-6, and IL-10. Serum levels of IFN-gamma and IL-2 were the highest in DF while in the most severe cases of DHF (i.e. grade IV) serum levels of IL-6 and IL-10 were maximum. Levels of IL-10 were negligible in patients with DF and levels of IFN-gamma were lowest in patients with DHF grade IV. The levels of TNF-a were higher in cases of DHF grades II, III, and IV and did not show the clear association pattern shown by IFN-gamma, IL-2, IL-4, IL-6, anti IL-10. The levels of IFN-gamma, IL-6 and TNF-alpha increased first while IL-4 and IL-10 levels increased during the 4th to 8th day of the illness. The most significant finding of the present study was a shift of the predominant Th1-type response observed in 66% of DF patients to the Th2-type response seen in the 71% of DHF grade IV patients, thus indicating a possible role for Th2 cells in the pathogenesis of DHF.