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Published ahead of print on April 15, 2004, doi:10.1164/rccm.200312-1647OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 2, July 2004, 175-180

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Submitted on December 3, 2003
Accepted on April 11, 2004

Cytokine Response Patterns, Exposure to Viruses,and Respiratory Infections in the First Year of Life

Christopher C Copenhaver1*, James E Gern1, Zhanhai Li2, Peter A Shult3, Louis A Rosenthal4, Lance D Mikus4, Carol J Kirk3, Kathy A Roberg1, Elizabeth L Anderson1, Christopher J Tisler1, Douglas F DaSilva1, Heidi J Hiemke1, Kevin Gentile1, Ronald E Gangnon2, and Robert F Lemanske, Jr5

1 Pediatrics, University of Wisconsin-Madison, Madison, WI, USA, 2 Biostatistics and Medical Informatics, Universtiy of Wisconsin-Madison, Madison, WI, USA, 3 University of Wisconsin-Madison, The Wisconsin State Laboratory of Hygiene, Madison, WI, USA, 4 Medicine, University of Wisconsin-Madison, Madison, WI, USA, 5 Pediatrics, University of Wisconsin-Madison, Madison, WI, USA; Medicine, University of Wisconsin-Madison, Madison, WI, USA

* To whom correspondence should be addressed. E-mail: cc.copenhaver{at}hosp.wisc.edu.

Daycare attendance and siblings are associated with viral-induced wheezing in children. Pre-existing immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. 285 children were enrolled in the Childhood Origins of Asthma project at birth and followed for at least one year. Cord blood and one-year mononuclear cells were stimulated with phytohemagglutinin, and cytokine response profiles were measured by enzyme-linked immubosorbent assay. Nasal lavage was performed for moderate-severe respiratory illnesses. Daycare attendance and/or siblings significantly increased the likelihood of contracting respiratory syncytial virus (1.5-1.6 fold increase) and rhinovirus (1.8-2.1 fold increase) and increased the risk of rhinovirus-induced wheezing (14-18% versus 2%, p<=0.011). Cord blood Interferon-gamma responses were inversely related to the frequency of viral respiratory infections (rs=-0.11, p=0.05), and more significant for subjects with high exposure to other children (rs=-0.27, p=0.028). The interval change in infantile Interferon-gamma responses was positively related to the frequency of viral infections in infancy (rs=0.12, p=0.047). These data suggest that neonatal IFN-{gamma} responses may influence anti-viral activity or may represent a marker of anti-viral immunity maturation. Conversely, the frequency of viral infections in infancy can influence Interferon-gamma responses.
Key words: Interferon-gamma, respiratory syncytial virus, daycare, sibling




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