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Published ahead of print on April 15, 2004, doi:10.1164/rccm.200312-1647OC
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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 175-180, (2004)
© 2004 American Thoracic Society

Original Article

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

Christopher C. Copenhaver, James E. Gern, Zhanhai Li, Peter A. Shult, Louis A. Rosenthal, Lance D. Mikus, Carol J. Kirk, Kathy A. Roberg, Elizabeth L. Anderson, Christopher J. Tisler, Douglas F. DaSilva, Heidi J. Hiemke, Kevin Gentile, Ronald E. Gangnon and Robert F. Lemanske, Jr.

Departments of Pediatrics, Biostatistics and Medical Informatics, and Medicine, University of Wisconsin, and Wisconsin State Laboratory of Hygiene, Madison, Wisconsin

Correspondence and requests for reprints should be addressed to Christopher C. Copenhaver, M.D., K4/910 University of Wisconsin Hospital, 600 Highland Avenue, Madison, WI 53792-9988. Email: cc.copenhaver{at}hosp.wisc.edu

Daycare attendance and siblings are associated with viral-induced wheezing in children. Preexisting immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. A total of 285 children were enrolled in the Childhood Origins of Asthma Project at birth and followed for at least 1 year. Cord blood and 1-year mononuclear cells were stimulated with phytohemagglutinin, and cytokine-response profiles were measured by enzyme-linked immunosorbent assay. Nasal lavage was performed for moderate to 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% vs. 2%, p = 0.011). Cord blood IFN-{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 IFN-{gamma} responses correlated positively with the frequency of viral infections in infancy (rs = 0.12, p = 0.047). These data suggest that neonatal IFN-{gamma} responses may influence antiviral activity, or may represent a marker of antiviral immunity maturation. Conversely, the frequency of viral infections in infancy can influence IFN-{gamma} responses.

Key Words: interferon-{gamma} • respiratory syncytial virus • daycare • sibling




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