Implications of dynamic changes among tumor necrosis factor-α (TNF-α), membrane TNF receptor, and soluble TNF receptor levels in regard to the severity of dengue infection

Tumor necrosis factor-α (TNF-α) and soluble TNF receptors (sTNFR1 and sTNFR2) have been implicated in infectious diseases. We investigated dynamic changes among TNF-α, membrane TNF receptors (mTNFR1 and mTNFR2), and sTNFR1 and sTNFR2 levels for patients with dengue hemorrhagic fever (DHF) and those not infected during a DEN-2 outbreak in southern Taiwan in 2002-2003. Patients with DHF showed the lowest levels of mTNFR1 and mTNFR2 expression. Multivariate analysis showed that a decrease in levels of mTNFR1 expression was the only factor significantly different between patients with DHF and those with dengue fever. Moreover, lower mTNFR1 expression was significantly correlated with higher plasma TNF-α levels, but not with sTNFR1 levels in patients with DHF. This finding suggests that a lower level of mTNFR1 expression in response to a higher plasma TNF-α level may be a pathogenic marker for early detection of DHF.