Cytokine Patterns During Dengue Shock Syndrome

Objective: To investigate the patterns of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, interferon-gamma (IFN-gamma) 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-alpha, IL-1beta and IL-1Ra were measured in duplicate by nonequilibrium radioimmunoassay (RIA); IFN-gamma 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-alpha and IL-1beta 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.