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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
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References
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