Inflammatory Cytokine Profile in Children With Severe Acute Respiratory Syndrome

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Abstract
Objective. To study the inflammatory cytokine profile in children with severe acute respiratory syndrome (SARS) and to investigate whether monoclonal antibody to tumor necrosis factor-α (TNF-α) could be considered for treatment of these patients. Methods. Plasma inflammatory cytokine concentrations (interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α) 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. Results. Plasma IL-1β 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-α, 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. Conclusions. Pediatric SARS patients have markedly elevated circulating IL-1β levels, which suggests selective activation of the caspase-1-dependent pathway. Other key proinflammatory cytokines, IL-6 and TNF-α, showed only mildly elevated levels at the initial phase of the illness. The current evidence does not support the use of TNF-α monoclonal antibody in this group of children.