Inflammatory cytokine profile in children with severe acute respiratory syndrome.

Abstract

To study the inflammatory cytokine profile in children with severe acute respiratory syndrome (SARS) and to investigate whether monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) could be considered for treatment of these patients. Plasma inflammatory cytokine concentrations (interleukin [IL]-1beta, IL-6, IL-8, IL-10, IL-12p70, and TNF-alpha) were monitored longitudinally on admission, immediately before corticosteroids, and 1 to 2 days and 7 to 10 days after the drug treatment in a cohort of pediatric patients (n = 8) with virologic confirmed SARS-associated coronavirus infection. None of the patients required mechanical ventilation or intensive care treatment. All children except 1 (patient 3) received corticosteroids. Plasma IL-1beta levels (excluding patient 3) were substantially elevated immediately before (range: 7-721 ng/L) and 7 to 10 days after (range: 7-664 ng/L) corticosteroid treatment. In contrast, the plasma concentrations of other key proinflammatory cytokines, including IL-6 and TNF-alpha, were not overtly increased in any of the patients throughout the course of illness. In addition, plasma IL-10 concentration was significantly lower 1 to 2 days and 7 to 10 days after corticosteroid treatment, compared with the immediate pretreatment level. Similarly, plasma IL-6 and IL-8 concentrations were significantly decreased 7 to 10 days after the drug treatment. Pediatric SARS patients have markedly elevated circulating IL-1beta levels, which suggests selective activation of the caspase-1-dependent pathway. Other key proinflammatory cytokines, IL-6 and TNF-alpha, showed only mildly elevated levels at the initial phase of the illness. The current evidence does not support the use of TNF-alpha monoclonal antibody in this group of children.