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Interleukin-10/Interleukin-5 Responses at Birth Predict Risk for Respiratory Infections in Children with Atopic Family History

¹ Telethon Institute for Child Health Research, and Centre for Child Health Research, Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia

Correspondence and requests for reprints should be addressed to P. G. Holt, M.D., Division of Cell Biology, Telethon Institute for Child Health Research, P.O. Box 855, West Perth, WA 6872, Australia. E-mail: khaas{at}ichr.uwa.edu.au

Rationale: Respiratory infections in early life are associated with risk for wheezing bronchiolitis, especially in children at high risk of atopy. The underlying mechanisms are unknown, but are suspected to involve imbalance(s) in host defense responses against pathogens stemming from functional immaturity of the immune system in this age group.

Objectives: To assess the contribution of eosinophil-trophic IL-5, and the potent antiinflammatory cytokine IL-10, to risk for infection in early life.

Measurements and Main Results: We prospectively monitored a cohort of 198 high-risk children to age 5 years, recording every acute respiratory infection episode and classifying them by severity. We measured cord blood T-cell capacity to produce IL-10 and IL-5, and related these functions to subsequent infection history. IL-10 and IL-5 were associated, respectively, with resistance versus susceptibility to infections. The greatest contrasting effects of these two cytokines were seen when they were considered in combination by generating IL-10/IL-5 response ratios for each subject. The low IL-10/high IL-5 T-cell response phenotype was strongly associated with susceptibility to all grades of acute respiratory infection, relative to the more resistant high IL-10/low IL-5 phenotype.

Conclusions: Excessive production of IL-5 by T cells at birth is associated with heightened risk for subsequent severe respiratory infections, and this risk is attenuated by concomitant IL-10 production. The underlying mechanisms may involve IL-10–mediated feedback inhibition of IL-5–dependent eosinophil-induced inflammation, which is a common feature of host antiviral responses in early life.

Key Words: infectious diseases • cord blood • cytokines

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Respiratory infections in early life are associated with risk for wheezing bronchiolitis, especially in children at high risk of atopy. The underlying mechanisms are unknown, but are suspected to involve imbalance(s) in host defense responses against pathogens stemming from functional immaturity of the immune system in this age group. What This Study Adds to the Field The balance between the capacity to produce the eosinophil-trophic cytokine IL-5 and the antiinflammatory cytokine IL-10 is strongly associated with infection risk in early life. High IL-5 is not a risk if balanced by sufficient IL-10 capacity.