Viral infections, cytokine dysregulation and the origins of childhood asthma and allergic diseases.
BACKGROUND
The origins of asthma and allergic disease begin in early life for many individuals. It is vital to understand the factors and/or events leading to their development.


METHODS
The Childhood Origins of Asthma project evaluated children at high risk for asthma to study the relationships among viral infections, environmental factors, immune dysregulation, genetic factors, and the development of atopic diseases. Consequently wheezing illnesses, viral respiratory pathogen identification, and in vitro cytokine response profiles were comprehensively evaluated from birth to 3 years of age, and associations of the observed phenotypes with genetic polymorphisms were investigated.


RESULTS
For the entire cohort, cytokine responses did not develop according to a strict T helper cell 1 or T helper cell 2 polarization pattern during infancy. Increased cord blood mononuclear cell phytohemagglutin-induced interferon-gamma responses of mononuclear cells were associated with decreased numbers of moderate to severe viral infections during infancy, especially among subjects with the greatest exposure to other children. In support of the hygiene hypothesis, an increased frequency of viral infections in infancy resulted in increased mitogen-induced interferon-gamma responses at 1 year of age. First year wheezing illnesses caused by respiratory viral infection were the strongest predictor of subsequent third year wheezing. Also, genotypic variation interacting with environmental factors, including day care, was associated with clinical and immunologic phenotypes that may precede the development of asthma.


CONCLUSIONS
Associations between clinical wheezing, viral identification, specific cytokine responses and genetic variation provide insight into the immunopathogenesis of childhood asthma and allergic diseases.
Friedlander
Samuel L
SL
Department of Medicine, Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, WI, USA. sl.friedlander@hosp.wisc.edu
Jackson
Daniel J
DJ
Gangnon
Ronald E
RE
Evans
Michael D
MD
Li
Zhanhai
Z
Roberg
Kathy A
KA
Anderson
Elizabeth L
EL
Carlson-Dakes
Kirstin T
KT
Adler
Kiva J
KJ
Gilbertson-White
Stephanie
S
Pappas
Tressa E
TE
Dasilva
Douglas F
DF
Tisler
Christopher J
CJ
Pleiss
Lisa E
LE
Mikus
Lance D
LD
Rosenthal
Louis A
LA
Shult
Peter A
PA
Kirk
Carol J
CJ
Reisdorf
Erik
E
Hoffjan
Sabine
S
Gern
James E
JE
Lemanske
Robert F
RF
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D012135:Respiratory Sounds / Q000209:etiology / Q000276:immunology; D012141:Respiratory Tract Infections / Q000150:complications* / Q000821:virology; D014777:Virus Diseases / Q000150:complications*
D016207:Cytokines