Inflammatory Cytokine Profile in Children With Severe Acute Respiratory Syndrome

Abstract

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-␣ (TNF-␣) could be considered for treatment of these patients.Methods. Plasma inflammatory cytokine concentrations (interleukin [IL]-1␤, IL-6, IL-8, IL-10, IL-12p70, and TNF-␣) 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-1␤ 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-␣, 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-1␤ levels, which suggests selective activation of the caspase-1-dependent pathway. Other key proinflammatory cytokines, IL-6 and TNF-␣, showed only mildly elevated levels at the initial phase of the illness. The current evidence does not support the use of TNF-␣ monoclonal antibody in this group of children. Pediatrics 2004;113:e7-e14. URL: http://www.pediatrics. org/cgi/content/full/113/1/e7; children, cytokines, SARS.

SARS: clinical presentation, transmission, pathogenesis and treatment options

“…Zhang et al [87] reported a fall in IL-8 levels, whereas Wang et al [89] reported no change in levels. Similarly, Ng et al [90] and Wang et al [89] reported no change in IL-6 levels. With TNF-α, the picture is very mixed, with several reports stating an increase in levels [77,86,89], some reporting no significant elevation [83,87,90] and others reporting a fall in levels [85].…”

SARS in Newborns and Children

“…Although a recent report suggests that young infants with SARS could become ill and require supplemental oxygen [26], young children, in general, develop a milder form of disease with a less aggressive clinical course than that of teenage and adult patients [6][7][8]. The understanding of the genome sequence of the SARS-CoV [27][28][29][30], the immunological profiles [15], and the natural history of the disease in different age groups [6-8, 12, 24] may hopefully facilitate the development of rapid and accurate diagnostic tests, treatments and vaccines to fight against this highly contagious and potentially devastating disease.…”

“…Whether children with mild or moderate SARS should be subjected to such potentially toxic treatment requires to be tested by future randomised clinical trials. Our latest study on cytokines does not support the use of TNF· monoclonal antibody for treatment of this category of patients [15]. New antiviral agents and immunomodulating drugs, such as kaletra and interferon-1ß, are currently under investigation.…”

“…There was marked elevation of circulating interleukin (IL)-1ß levels suggesting selective caspase-1-dependent pathway activation in infected macrophages [15]. Conversely, IL-6 and tumour necrosis factor (TNF)·, which were markedly increased in avian H5N1 influenza infection [16,17], were only mildly raised in the acute phase of SARS [15].…”

Chemokine response in children with SARS

“…1 In brief, case 3 was the only patient who did not receive corticosteroid treatment. Cases 2 and 6 required pulse methylprednisolone, and case 6 also received intravenous ribavirin.…”