Cytokine patterns during dengue shock syndrome

Abstract

Objective. To investigate the patterns of tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), IL-6, interferon-c (IFN-c) and interleukin-1 receptor antagonist (IL-1Ra) during the course of dengue shock syndrome. Design. Prospective clinical study. Setting. Pediatric Intensive Care Unit, Dr. Kariadi Hospital, the university hospital of Diponegoro University, Semarang, Indonesia. Patients. Fifty children with dengue shock syndrome. Measurements. The plasma concentration and the ex vivo production, with and without lipopolysaccharide (LPS), of TNF-a, IL-1b and IL-1Ra were measured in duplicate by nonequilibrium radioimmunoassay (RIA); IFN-c and IL-6 were measured by ELISA. Results. During the acute phase, the plasma concentrations and the ex vivo production without LPS of IL-1Ra were considerably elevated and returned to normal on recovery. However, the ex vivo LPS-stimulated production of the proinflammatory cytokines TNF-a and IL-1b were considerably depressed. Also, these concentrations returned towards normal on recovery. In non-survivors, the plasma concentrations of IL-6 and IL-1Ra were significantly higher than in survivors (p < 0.00001 and p = 0.0005, respectively). In addition, the ex vivo production of IL-1Ra in non-survivors was significantly higher than in survivors, both without LPS stimulation (p = 0.0008) and with LPS (p < 0.004). IL-1Ra was significantly associated with mortality (p = 0.007). Conclusion. Since IL-1Ra was significantly associated with mortality, this measurement may be used as an index of disease severity in dengue shock syndrome.