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Published ahead of print on May 28, 2003, doi:10.1164/rccm.200210-1148OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 6, September 2003, 633-639

A more recent version of this article appeared on September 15, 2003
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Submitted on October 16, 2002
Accepted on May 27, 2003

Type 1 and Type 2 Cytokine Imbalance inAcute Respiratory Syncytial Virus Bronchiolitis

Julian P Legg1*, Imran R Hussain1, Jill A Warner1, Sebastian L Johnston2, and John O Warner1

1 Infection, Inflammation and Repair Division, University of Southampton, Southampton, Hampshire, United Kingdom, 2 Respiratory Medicine, Imperial College of Science Technology and Medicine, National Heart and Lung Institute, London, United Kingdom; Infection, Inflammation and Repair Division, University of Southampton, Southampton, Hampshire, United Kingdom

* To whom correspondence should be addressed. E-mail: julianlegg{at}yahoo.co.uk.

We examined the in-vivo immune response of infants to natural respiratory syncytial virus infection through analysis of cytokine levels in nasal lavage fluid and from stimulated peripheral blood mononuclear cells. 88 babies with at least one atopic, asthmatic parent were prospectively studied through their first winter. 28 infants had an URTI where RSV was detected of whom 9 developed signs of acute bronchiolitis. Nasal lavage specimens were assayed for interferon-{gamma}, IL-4, IL-10 and IL-12 and the RSV load determined by quantitative PCR. mRNA was extracted from stimulated peripheral blood mononuclear cells and Interferon-{gamma}, IL-4, IL-12 and IL-18 mRNA levels determined by PCR. Cytokine profiles were analyzed in relation to clinical outcome. The IL-4/Interferon-{gamma} ratio for infants with acute bronchiolitis was elevated in nasal lavage fluid on both days 1-2 (p=0.014) and days 5-7 (p=0.001) of the illness compared with infants with URTI alone. Those with acute bronchiolitis demonstrated a higher IL-10/IL-12 ratio (p=0.0015) on days 1-2. IL-18 mRNA levels were reduced (p=0.019) and the IL-4/Interferon-{gamma} ratio elevated (p=0.01) in stimulated peripheral blood mononuclear cells from infants with acute bronchiolitis. There was no difference in initial RSV load. These data strongly implicate excess type 2 and/or deficient type 1 immune responses in the pathogenesis of RSV bronchiolitis.
Key words: Respiratory Syncytial Virus Infections, Nasal Lavage Fluid, Th1 Cells, Th2 Cells, Infant




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