ArticlesRelation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma
Introduction
Endotoxin is derived from the cells walls of gram-negative bacteria, and can be detected in house dust in widely varying concentrations.1, 2, 3 The potential of endotoxin to abrogate the development of allergy can be appreciated by considering the mechanisms of endotoxin-induced immune responses. In studies on human peripheral blood cells, endotoxin is a potent inducer of the type 1 cytokines interferon γ and interleukin 12.4, 5 Interferon γ is counter-regulatory to the development of lymphocytes that produce the type 2 cytokines (interleukins 4, 5, 13), that underlie the immune pathogenesis of allergic diseases.6
On this basis, chronic endotoxin exposure in infants (ie, before polarised T-cell responses are established), might be expected to protect against allergen sensitisation by continually enhancing type 1 lymphocyte development. Indeed, in young children, increased interferon-γ production in vitro by peripheral-blood mononuclear cells has been associated with a lack of specific allergen sensitisation to mites, and with decreased rates of asthma.7 Conversely, decreased interferon-γ production in children, and even newborn babies, has been associated with increased atopy.8, 9, 10, 11 We aimed to find out whether chronic environmental endotoxin exposure mitigates the development of allergen sensitisation in young asthma-prone children by enhancement of type 1 immunity.
Section snippets
Participants
61 asthma-prone infants were recruited at enrolment in a separate study on the prevention of chronic asthma in young children, funded by the US National Institutes of Health (#R18-AI41137). Enrolment criteria were: age 9–24 months, three physician-documented wheezing episodes, and low socioeconomic status; these characteristics have been denned as high-risk features for the development of asthma.12, 13 The study was approved by the National Jewish Medical & Research Center Institutional Review
Results
The 61 asthma-prone infants were divided into those who were positive on the skin-prick test (n=10) and those who were negative (n=51). The ten allergen-sensitised infants showed no response to the negative control, but at least one positive skin test to major indoor inhalant allergens (nine infants) and/or food allergens (four infants). The nine aeroallergen-sensitive infants were skin-test positive for dust mites (six infants), cat (three), dog (one), and mouse (one); the four food-sensitive
Discussion
The potential for environmental exposures in early life to affect the prevalence of atopy has been suggested by epidemiological reports of substantial variation in the prevalence of allergen sensitisation and the atopic diseases in children of common ethnic or genetic descent living under different conditions.22, 23, 24 Certain microbial infections that are presumably inducers of type 1 immune responses (eg, measles, hepatitis A), have been associated with decreased rates of atopy and asthma.25
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