Circulating levels of tumour necrosis factor-alpha & interferon-gamma in patients with dengue & dengue haemorrhagic fever during an outbreak.

ABSTRACT

BACKGROUND & OBJECTIVE: Dengue haemorrhagic fever (DHF) is a severe illness caused by dengue viruses, the pathogenesis of which is not fully understood. Immune enhancement caused by cytokines, interferon and activated complement system is one of the hypotheses proposed to explain the haemorrhagic form of disease. This study was undertaken to investigate the role of pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in dengue infection, and their possible association with disease severity. METHODS: Blood samples were collected from 60 patients; 28 patients of DF and 32 of DHF (clinically categorized into DF or DHF as per WHO criteria) from September to November 2003 at Delhi. Fifteen healthy individuals were included as control. All the patients were confirmed positive for dengue infection by serology or by reverse transcriptase-polymerase chain reaction (RT-PCR). Serum levels of TNF-alpha and IFN-gamma were determined by ELISA. RESULTS: The levels of both the cytokines were significantly elevated in the disease group as compared to the control group. Significantly higher levels of TNF-alpha; 258.02 pg/ml (P<0.005) were seen in patients having secondary infection, while patients with primary infection had higher level of IFN-gamma; 29.47 pg/ml (P<0.005). TNF-alpha was elevated in the later phase of illness, while IFN-gamma was elevated in early phase also. INTERPRETATION & CONCLUSION: Overproduction of TNF-alpha during secondary infection may have a role in immunopathogenesis of DHF, however, study of other cytokines produced along with IFN-gamma;, during the course of dengue infection is required to know the specific role of IFN-gamma in DI.