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COMMENTS

Determinants of Reduced Interferon Gamma Expression in Severe Respiratory Syncytial Virus Disease

Luton&Dunstable Hospital NHS Foundation Trust, Luton, LU40DZ United Kingdom

¹To whom requests for reprints should be addressed at Luton&Dunstable Hospital, NHS Foundation Trust, Lewsey Road, Luton, LU40DZ United Kingdom. E-mail: michael_eisenhut{at}yahoo.com

Scagnolari C et al. reported on an inverse relationship of expression of interferon (IFN) induced genes 2'-5' oligoadenylate synthetase, dsRNA-activated protein kinase R and P56 in cells from nasopharyngeal washes of infants with acute bronchiolitis and severity of disease (1). More severe illness was associated with lower expression of IFN induced genes. The authors thought there was an absence of studies demonstrating IFN in sera or secretions of infants with bronchiolitis. A recent study investigated the role of IFN gamma and found that nasopharyngeal IFN gamma concentrations were significantly lower in more severe compared to mild respiratory syncytial virus bronchiolitis as opposed to interleukin-9 levels, which were not significantly different (2). IFN gamma concentrations did not seem to relate to viral load in nasopharyngeal secretions. Supporting a role of the IFN gamma response in disease severity were previous studies, which showed a lower production of IFN gamma in phytohaemagglutinin-stimulated whole blood cultures in ventilated compared to non-ventilated infants with RSV bronchiolitis (3). More detailed investigations by other groups revealed a reduced IFN gamma expression in peripheral blood mononuclear cells of infants with severe or moderately severe compared to moderately severe or mild bronchiolitis respectively (4, 5). Against a host factor in IFN gamma production was that IFN gamma genotype (high and low producer) was not associated with hospitalisation of RSV disease or a score of respiratory disease severity (6). Previous studies investigating the specific role of the virus suggested that the suppression of IFN gamma production is more pronounced with RSV infection compared to other respiratory viruses (7, 8). RSV infection of dendritic cells reduced the rate of IFN gamma production in co-cultured autologous naïve T cells stimulated by a superantigen (9). Future studies investigating whether host or viral factors determine IFN gamma response and disease severity in respiratory syncytial virus infection need to examine whether the RSV genotype is associated with a suppression of IFN gamma production or host factors like oestrogen levels which upregulate IFN gamma production (10) potentially explaining the consistent predominance of males in large studies of patients with severe RSV bronchiolitis (11).

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

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2. Semple MG, Dankert HM, Ebrahimi B, Correia JB, Booth JA, Stewart JP, Smyth RL, Hart CA. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance P. PloS ONE 2(10):e1038.
3. Bont L, Heijnen CJ, Kavelaars A, Van Aalderen WMC, Brus F, Draaisma JThM, Geelen SM, Van Vught HJ, Kimpen JLL. Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J 14:144–149, 1999.[Abstract]
4. Aberle JH, Aberle SW, Dworzak MN, Mandl CW, Rebhandl W, Vollnhofer G, Kundi M, Popow-Kraupp T. Reduced interferon- expression in peripheral blood mononuclear cells of infants with severe respiratory syncytial virus disease. Am J Respir Crit Care Med 160: 1263–1268, 1999.[Abstract/Free Full Text]
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11. Falagas ME, Mourtzoukou EG, Vardakas KZ. Sex differences in the incidence and severity of respiratory tract infections. Resp Med 101: 1845–1863, 2007.[Medline]

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