Elsevier

The Lancet

Volume 355, Issue 9216, 13 May 2000, Pages 1680-1683
The Lancet

Articles
Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma

https://doi.org/10.1016/S0140-6736(00)02239-XGet rights and content

Summary

Background

Bacterial endotoxin is known to induce interferon -γ and interleukin 12 production, and therefore has the potential to decrease allergen sensitisation. To find out the role of early chronic endotoxin exposure in the development of allergen sensitisation and asthma, we compared concentrations of endotoxin in house dust with allergen sensitisation in infants at high risk for developing asthma.

Methods

61 infants 9–24 months old with at least three physician-documented episodes of wheezing were studied. Concentrations of house-dust endotoxin and allergens were measured in the infants' homes. Allergen sensitisation was measured by skin-prick testing with a panel of common inhalant and food allergens. In a subset of these infants, proportions of T lymphocytes producing interferon γ, and interleukins 4, 5, and 13 were calculated by cell-surface and intracellular cytokine staining, with flow cytometry.

Findings

House-dust endotoxin concentrations ranged from 104 to 10 000 endotoxin units (EU) per ml (geometric mean 912 EU/mL). Concentrations did not vary significantly over a 6-month interval. Ten infants (16%) were sensitised to at least one allergen. The homes of allergen-sensitised infants contained significantly lower concentrations of house-dust endotoxin than those of non-sensitised infants (mean 468 vs 1035 EU/mL, respectively; p=0·01). Increased house-dust endotoxin concentrations correlated with increased proportions of interferon-y-producing CD4 T cells (p=0·01). Such concentrations did not correlate with proportions of cells that produced interleukins 4, 5, or 13.

Interpretation

This study may provide the first direct in-vivo evidence that indoor endotoxin exposure early in life may protect against allergen sensitisation by enhancing type 1 immunity.

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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