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ELECTRONIC ARTICLE:
Pak C. Ng, Christopher W.K. Lam, Albert M. Li, Chun K. Wong, Frankie W.T. Cheng, Ting F. Leung, Ellis K.L. Hon, Iris H.S. Chan, Chi K. Li, Kitty S.C. Fung, and Tai F. Fok
Inflammatory Cytokine Profile in Children With Severe Acute Respiratory Syndrome
Pediatrics 2004; 113: e7-e14 [Abstract] [Full text] [PDF]
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P3Rs published:

[Read P3R] SARS, corticosteroids, and TNF-alpha
Edward L. Tobinick   (15 February 2004)
[Read P3R] TNF-alpha in SARS
Pak C. Ng, Christopher W. K. Lam, Ting F. Leung.   (25 February 2004)

SARS, corticosteroids, and TNF-alpha 15 February 2004
Next P3R Top
Edward L. Tobinick,
Physician
Assistant Clinical Professor of Medicine, UCLA

Send letter to journal:
Re: SARS, corticosteroids, and TNF-alpha

etmd{at}ucla.edu Edward L. Tobinick

Please note competing interests: The author has filed a patent application concerning the use of TNF-alpha antagonists for the treatment of SARS, and has an issued U.S. patent, 6,419,934, concerning the use of TNF-alpha antagonists for the treatment of influenza.

To the Editor:

This study by Ng, et. al., involves a small cohort (n=8) of children with SARS, all but one of whom received treatment with both ribavirin and corticosteroids. Serial measurement of several cytokines was performed. The authors conclude that “the current evidence does not support the use of monoclonal antibody to TNF-alpha for treatment of children with SARS.”

This conclusion, if based on the results of this current study, suffers from a significant shortcoming i.e. all patients except one were treated with corticosteroids and ribavirin. This treatment regimen may reasonably have been expected to change the cytokine patterns in these patients. Therefore it would seem that it might be more accurate to conclude “the current evidence from this study does not support the use of monoclonal antibody to TNF-alpha for treatment of children with SARS who have received corticosteroids and ribavirin”.

Caution is necessary in extrapolating the results of this small study to SARS in adults. None of these patients required mechanical ventilation or intensive care treatment, and there was no mortality. Cytokine patterns in adults may be different, and may account for the increased mortality from SARS seen in older patients.

Late adverse effects from corticosteroid treatment in SARS patients have been reported (osteonecrosis, avascular necrosis), an adverse effect which is not expected from the use of biologic TNF inhibitors. It is perhaps a disservice to consider abandoning the study of the use of biologic TNF inhibitors as an alternative to high dose corticosteroids for the treatment of SARS, particularly in adults with high pre-treatment serum levels of TNF-alpha. Further study is warranted, not only in SARS but also in H5N1 influenza, in which the role of TNF-alpha has been more clearly implicated.

TNF-alpha in SARS 25 February 2004
Previous P3R Top
Pak C. Ng,
Professor
Department of Paediatrics, The Chinese University of Hong Kong,
Christopher W. K. Lam, Ting F. Leung.

Send letter to journal:
Re: TNF-alpha in SARS

pakcheungng{at}cuhk.edu.hk Pak C. Ng, et al.

The cohort of 8 children reported in our article (1) comprised all the pediatric cases with severe acute respiratory syndrome (SARS) admitted to the Prince of Wales Hospital. It represented about 10% of all pediatric SARS patients in Hong Kong. Their presentation and clinical course were 'typical' of the majority (96%) of children infected with SARS -associated coronavirus. Only a small percentage (4%) of children with SARS required mechanical ventilation or intensive care treatment in Hong Kong. Despite the fact that all but one child in our cohort received corticosteroid treatment, their cytokine profiles were checked during clinical deterioration and immediately prior to corticosteroid administration. Unlike interleukin-1 beta, tumor necrosis factor-alpha (TNFa) concentration was not substantially raised in corticosteroid treated or untreated children at the time of deterioration. In addition, our findings are very similar to those of adult SARS patients with moderate disease (2). Although in the latter study all patients were also treated with oral prednisolone and ribavirin, there was no significant difference in TNFa concentration before and after corticosteroid. Many patients in either studies started corticosteroid treatment in the second week of illness (1,2), and TNFa level should have been increased at this stage. Thus far, there was no evidence to suggest a marked elevation in plasma TNFa concentration in both children and adult patients with mild and moderate disease (1,2). These findings did not support the proposal by Tobinick, in his letter published in this issue, that the use of TNFa inhibitors might be useful in mild and moderately affected cases. It is known that different viral infection produces different pattern of immunological response. The cytokine profile in our SARS patients is in sharp contrast to that observed in patients with H5N1 influenza virus infection in which significant up-regulation of TNFa could be detected. As mentioned in our study, we also cautioned extrapolating the results to severe cases of SARS. Further studies are required to elucidate the cytokine profile and the therapeutic potential of biologic TNFa inhibitors in SARS patients with severe disease.

References

1. Ng PC, Lam CWK, Li AM, et al. Inflammatory cytokine profile in children with severe acute respiratory syndrome. Pediatrics 2004;113:e7- e14.

2. Wong CK, Lam CWK, Wu AKL, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol 2004 (in press).