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Experimental Biology and Medicine 233:495 (2008)
© 2008 by the Society for Experimental Biology and Medicine

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COMMENTS

Determinants of Reduced Interferon Gamma Expression in Severe Respiratory Syncytial Virus Disease: The Authors Respond

Carolina Scagnolari and Guido Antonelli1

Department of Experimental Medicine – Section of Virology, "Sapienza" University of Rome, 00185 Rome, Italy

1 To whom requests for reprints should be addressed at Department of Experimental Medicine – Section of Virology, "Sapienza" University of Rome, V.le di Porta Tiburtina 28, 00185 Rome, Italy. E-mail: guido.antonelli{at}uniroma1.it

We agree with Dr. Eisenhut that a definite conclusion on the role of interferon (IFN) on the natural history of acute bronchiolitis in infants cannot be reached without taking into account the production of IFN gamma. Indeed, as Dr. Eisenhut correctly says, it is known that host factors together with viral factors may affect the severity of such a disease through the modulation of cytokine expression, including IFN gamma.

As we pointed out, one of the important limitations of the study was the lack of correlation between the level of expression of IFN-induced genes and the level of the different types of IFN in nasopharyngeal washes. Indeed, we did not address the question of whether the IFN-induced genes were associated with the production of type-I, -II and/or -III IFN. However, it should be noted that the nasopharyngeal washes on which all our experiments were performed presumably contained IFNs at very low concentrations levels and, considering the amounts of sampling fluid, these should be below the detection limit of any assay. Moreover, according to other studies, accurate quantification of cytokines in nasal washings has proved difficult because of the unpredictable dilution of secretion by the diluent at the time of sample collection (1, 2).

Further, most of the experiments cited by Dr. Eisenhut were carried ex vivo or in vitro using peripheral blood mononuclear cells (PBMC). The results are extremely interesting but, in our context, examining the level of expression of IFN in PBMC, other than to be more binding from an ethical viewpoint, would mean deviating somewhat from the subject in hand. Directly related to this, a discrepancy has been shown to exist between IFN gamma production from PBMCs and nasal secretions from infants with acute bronchiolitis, which suggests that peripheral blood samples are not reliable for airway inflammation evaluation (3).

In conclusion, we consider that our study, although far from being exhaustive and conclusive and despite the above limitations, has value: viz: it confirms that other respiratory viruses, especially rhinovirus, may contribute to the pathogenesis of bronchiolitis; it demonstrates that there is strong activation of the IFN system in respiratory tract; and, finally, it suggests that the severity of bronchiolitis is inversely correlated to the level of expression of IFN-induced genes whatever type of IFN is produced.

Footnotes

We welcome comments by our readers reflecting agreement or disagreement with the material published in Experimental Biology and Medicine and, at the discretion of the Editor-in-Chief, will publish such comments. The statements and opinions contained in the articles of Experimental Biology and Medicine are solely those of the individual authors and contributors and not of the Society for Experimental Biology and Medicine.

References

  1. Heikkinen T, Shenoy M, Goldblum RM, Chonmaitree T. Quantification of cytokines and inflammatory mediators in samples of nasopharyngeal secretions with unknown dilution. Pediatr Res 45(2):230, 1999.[Medline]
  2. Riechelmann H, Deutschle T, Friemel E, Gross HJ, Bachem M. Biological markers in nasal secretions. Eur Respir J 21(4):600–605, 2003.[Abstract/Free Full Text]
  3. Pitrez PM, Ponzi D, Machado DC, Bauer ME, Jones MH, Stein RT. Discrepancy between cytokine production from peripheral blood mononuclear cells and nasal secretions among infants with acute bronchiolitis. Ann Allergy Asthma Immunol 92(6):659–662, 2004.[Medline]




This Article
Right arrow Full Text (PDF) Free
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Right arrow Articles by Scagnolari, C.
Right arrow Articles by Antonelli, G.
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PubMed
Right arrow Articles by Scagnolari, C.
Right arrow Articles by Antonelli, G.


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