PURPOSE OF STUDY.
To determine whether decreased Toll-like receptor (TLR)-mediated cytokine production at 1 month of age is associated with development of atopic dermatitis (AD) or respiratory syncytial virus lower respiratory tract infection (RSV LRTI). The first month of life is a period of rapid development of the TLR system, and disruption of this development early in life may lead to dysfunction of innate and adaptive immunity and predispose to atopy.
Healthy term neonates (N = 291) from a birth cohort study in the Netherlands. Subjects were enrolled prospectively and followed for 12 months.
At 1 month of age, subjects’ serum concentrations of immune cells were measured by absolute leukocyte count and flow cytometry. After TLR stimulation in vitro, cytokine responses were measured via ELISA. Subjects were assessed for subsequent development of AD and RSV LRTI during the first year of life. AD diagnosis was determined by physician questionnaire at 1 year, and RSV LRTI was determined by reported respiratory symptoms and RSV-positive nasal-throat sample.
Overall, 15% of subjects developed AD and 14% developed RSV LRTI during the first year of life. AD was significantly associated with increased natural killer cells, decreased basophils, and dendritic cells and a 1.8-fold lower TL4-mediated interleukin (IL)-10 production (P < .001). RSV LRTI was not associated with either significant changes in the innate immune cell profile or TLR-mediated cytokine production.
This study found the development of AD, but not RSV LRTI, to be associated with distinct differences in the innate immune system early in life. Decreased TLR-4–mediated IL-10 production may have a causal role in development of AD.
IL-10 is a key regulatory cytokine of the immune system. This study hypothesizes that decreased IL-10–mediated regulation of innate responses may contribute to development of atopic skin disease. Further studies are needed to validate these results and investigate the basic mechanisms of neonatal TLR-mediated IL-10 production, as doing so may identify potential targets for prevention and/or treatment of AD.
- Copyright © 2012 by the American Academy of Pediatrics