Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis

Dengue virus produces a mild acute febrile illness, dengue fever (DF) and a severe illness. dengue hemorrhagic fever (DHF). The characteristic feature of DHF is increased capillary permeability leading to extensive plasma lea kage in serous cavities resulting in shock. The pathogenesis of DHF is not fully understood. This paper presents a cascade of cytokines, that in our v iew, may lead to DHF. The main feature is the early generation of a unique cytokine, human cytotoxic factor (hCF) that initiates a series of events le ading to a shift from Th1-type response in mild illness to a Th2-type respo nse resulting in severe DHF. The shift from Th1 to Th2 is regulated by the relative levels of interferon-gamma and interleukin (IL)-10 and between IL- 12 and transforming growth factor-beta, which showed an inverse relationshi p in patients with DF. (C) 2000 Published by Elsevier Science B.V. on behal f of the Federation of European Microbiological Societies.