Association of Intracellular T(H)1-T(H)2 Balance in CD4+ T-cells and MIP-1α in CD8+ T-cells with Disease Severity in Adults with Dengue

BACKGROUND: We tested the hypothesis that dengue haemorrhagic fever (DHF) is associated with a T(H)1-skewed immune response as opposed to dengue fever (DF). METHODS: We estimated intracellular (in T-cells) and serum levels of designate T(H)1/T(H)2 cytokines [interferon-γ (IFN-γ), interleukin-4 (IL-4), and tumor necrosis factor-α] and macrophage inflammatory protein-1α (MIP-1α) at admission, 48 h, and day 5 in 20 adults with dengue (DF=10, DHF=10) and 10 dengue-naïve healthy controls. RESULTS: At admission, intracellular IFN-γ/IL-4 ratio in CD4+ T-cells and proportion of MIP-1α-positive CD8+ T-cells were significantly higher in patients with DHF [7.21 (5.36~10.81) vs. 3.04 (1.75~4.02); p=0.011 and 6.2% (3.2~8.2%) vs. 2.4% (2.0~3.6%); p=0.023]. The latter showed a significant positive correlation with IFN-γ/IL-4 ratio in CD4+ T-cells (Spearman's rho=0.64; p=0.003), percentage-change in haematocrit (rho=0.47; p=0.048), and serum alanine aminotransferase level (rho=0.61; p=0.009). CONCLUSION: We conclude that DHF is associated with a T(H)1-skewed immune response. Further, MIP-1α in CD8+ T-cells is an important immunologic correlate of disease severity in dengue.