Bidirectional interactions between viral respiratory illnesses and cytokine responses in the first year of life.
BACKGROUND
Viral infections are the major cause of acute wheezing illnesses in childhood. Variations in immunologic responses at birth may be determinants of the risk of acquiring these illnesses.


OBJECTIVE
To determine the immunologic risk factors for virus-induced wheezing in high-risk infants.


METHODS
The study involves 285 children with a parental history of asthma and/or respiratory allergies. Mononuclear cells obtained at birth (umbilical cord blood) and at 1 year of age were incubated with phytohemagglutinin, respiratory syncytial virus, or rhinovirus, and supernatants were analyzed for IL-5, IL-10, IL-13, and IFN-gamma. Nasal secretions obtained at well child visits and during respiratory illnesses were analyzed for common respiratory viruses.


RESULTS
Respiratory syncytial virus-induced wheezing was associated with reduced phytohemagglutinin-induced IL-13 responses (medians, 213 vs 304 pg/mL; P = .026) from cord blood cells, and similar trends were found for wheezing in general. Furthermore, median IL-13 responses diminished by 28% in non-wheezing children by age 1 year, versus only 3% in wheezing children (P = .013). Children with > or =2 episodes of wheezing had lower phytohemagglutinin-induced IFN-gamma responses and were less likely to have rhinovirus-induced IFN-gamma responses at birth (P < .05). Finally, children with measurable cord blood IFN responses to respiratory syncytial virus were less likely to wheeze in their first year (odds ratio, 0.43 [0.23, 0.79]).


CONCLUSIONS
In children with a family history of allergies and/or asthma, mononuclear cell phytohemagglutinin-induced IL-13 and virus-induced IFN-gamma responses at birth are indicative of the risk for wheezing in the first year of life.
Gern
James E
JE
Department of Pediatrics, University of Wisconsin Hospital, 600 Highland Avenue, Madison, WI 53792, USA.
Brooks
G Daniel
GD
Meyer
Patricia
P
Chang
Andy
A
Shen
Kunling
K
Evans
Michael D
MD
Tisler
Chris
C
Dasilva
Douglas
D
Roberg
Kathy A
KA
Mikus
Lance D
LD
Rosenthal
Louis A
LA
Kirk
Carole J
CJ
Shult
Peter A
PA
Bhattacharya
Abhik
A
Li
Zhanhai
Z
Gangnon
Ronald
R
Lemanske
Robert F
RF
D003139:Common Cold / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D010835:Phytohemagglutinins / Q000494:pharmacology; D012135:Respiratory Sounds / Q000209:etiology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D012307:Risk Factors; D014777:Virus Diseases / Q000276:immunology*
D016207:Cytokines; D018793:Interleukin-13; D010835:Phytohemagglutinins; D007371:Interferon-gamma