PURIFICATION AND PATHOGENICITY OF THE CYTOTOXIC FACTOR FROM THE CASES OF DENGUE HAEMORRHAGIC FEVER

摘要

Pathogenesis of dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is not yet clear in spite of extensive efforts. Here we report the discovery of a cytotoxic cytokine (hCF) in the sera of the patients with DHF/DSS which is capable of increasing vascular permeability in mice. The presence of hCF was detected in the sera of the cases of DHF by dot blot test. hCF was purified from the sera of 34 dot blot-positive patients of DHF by ion-exchange chromatography followed by high performance liquid chromatography. The eluted hCF was cytotoxic to normal mouse spleen cells, had a molecular weight of 43 kD and an isoelectric point of pH 4.5-5. It reacted in dot blot and Western blot tests with anti-mouse cytotoxic factor (mCF) and anti-hCF-antisera. The effect of hCF on the capillary permeability and the blood-brain barrier of mice was investigated using leakage of Evans blue dye-bound plasma proteins. It was observed that inoculation of the hCF in mice increased the capillary permeability and damaged the blood-brain barrier in a dose-dependent manner. This is the first evidence of the presence of cytotoxic factor (hCF), a homologue of mCF, in the sera of the cases of DHF/DSS which can cause reversible damage to capillaries. [References: 23]