Pathophysiologic and Prognostic Role of Cytokines in Dengue Hemorrhagic Fever

Abstract

Dengue shock syndrome is a severe complication of dengue hemorrhagic fever (DHF), characterized by a massive increase in vascular permeability. Plasma cytokine concentrations were prospectively studied in 443 Vietnamese children with DHF, of whom 6 died. Shock was present in 188 children on admission to hospital, and in 71 children it developed later. Contrary to expectations, certain inflammatory markers (interleukin-6 and soluble intercellular adhesion molecule-1) were lower in the group with shock, and this may reflect the general loss of protein from the circulation due to capillary leakage. Only soluble tumor necrosis factor receptor (TNFR) levels showed a consistent positive relationship with disease severity. In patients with suspected DHF without shock, admission levels of sTNFR-75 in excess of 55 pg/mL predicted the subsequent development of shock, with a relative risk of 5.5 (95% confidence interval, 2.3-13.2). Large-scale release of soluble TNFR may be an early and specific marker of the endothelial changes that cause dengue shock syndrome.

Inflammatory mediators in dengue virus infection in children: interleukin-6 and its relation to C-reactive protein and secretory phospholipase A2.

“…After correction for albumin levels as a marker of capillary leakage, no significant correlation between levels of IL-6 and disease severity was found. 22 The maximal level of IL-6 in our study was less than 110 pg/ml. Similar IL-6 levels have been reported in another study in DHF.…”

“…[24][25][26] In one study CRP levels were measured in addition to IL-6 levels but their correlation was not assessed. 22 To our knowledge, type II sPLA2 has been measured only in one dengue study, in which elevated levels were present in 90% of these patients. No correlation with other mediators was mentioned.…”

“…[15][16][17][18] There are only limited data on the importance of IL-6 in dengue-infected patients. [19][20][21][22][23] These data are somewhat conflicting. Some studies show a correlation between severity of illness and IL-6 levels, i.e., highest levels in DHF/DSS.…”

“…Some studies show a correlation between severity of illness and IL-6 levels, i.e., highest levels in DHF/DSS. [19][20][21] In one large prospective study, 22 IL-6 levels tended to be lower in patients in shock than those not in shock. Also there are discrepancies with respect to the proportion of patients showing elevated IL-6 levels.…”

Correlation of IFN-Inducible Protein 10 Levels in Sera with Disease Severity and Clinical Outcome of the Dengue Patients

“…Platelet abnormalities correlate with the severity of the hemorrhage. Patients with GI bleeding normally showed significantly lower platelet counts compared to those without GI bleeding [9,10] . However, the platelet counts in our DF, DHF and DSS patients were no significant difference, which may be related to our patients without GI bleeding symptom (Table 1).…”