Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases
ABSTRACT The unparalleled burden of a diverse range of chronic noncommunicable diseases (NCDs) is a major global challenge in the 21st century. Chronic low-grade inflammation is a common feature of virtually all NCDs, indicating a central role of the immune system. Furthermore, as the most common and earliest-onset NCD, the epidemic of allergic diseases points to specific vulnerability of the developing immune system to modern environmental change. Indeed, many environmental risk factors implicated in the rise of other NCDs have been shown to mediate their effects through immune pathways. The innate immune system provides a clear example of this convergence, with evidence that physical activity, nutrition, pollutants, and the microbiome all influence systemic inflammation through Toll-like receptor pathways (notably Toll-like receptor 4), with downstream effects on the risk of insulin resistance, obesity, cardiovascular risk, immune diseases, and even mood and behavior. Common risk factors will likely mean common solutions, and interdisciplinary strategies to promote immune health should be an integral part of NCD prevention, with a greater focus early in the life course before disease processes are established. In this context allergic disease provides a very important early target to assess the effectiveness of environmental strategies to reduce immune dysregulation.
Full-textDOI: · Available from: Susan L Prescott, Jan 30, 2015
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ABSTRACT: An ability to detect subtle signs of sickness in others would be highly beneficial, as it would allow for behaviors that help us avoid contagious pathogens. Recent findings suggest that both animals and humans are able to detect distinctive odor signals of individuals with activated innate immune responses. This study tested whether an innate immune response affects a person's walking speed and whether other people experience that person as less healthy. 43 subjects watched films of persons who were experiencing experimental immune activation, and rated the walking individuals in the films with respect to health, tiredness, and sadness. Furthermore, the walking speed in the films was analyzed. After LPS injections, participants walked more slowly and were perceived as less healthy and more tired as compared to when injected with placebo. There was also a trend for the subjects to look sadder after LPS injection than after placebo. Furthermore, there were strong associations between walking speed and the appearance of health, tiredness, and sadness. These findings support the notion that walking speed is affected by an activated immune response, and that humans may be able to detect very early signs of sickness in others by merely observing their gait. This ability is likely to aid both a "behavioral immune system", by providing more opportunities for adaptive behaviors such as avoidance, and the anticipatory priming of biochemical immune responses. Copyright © 2015. Published by Elsevier Inc.Brain Behavior and Immunity 03/2015; DOI:10.1016/j.bbi.2015.03.007 · 6.13 Impact Factor
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ABSTRACT: Allergic disease can be viewed as an early manifestation of immune dysregulation. Environmental exposures including maternal inflammation, diet, nutrient balance, microbial colonisation and toxin exposures can directly and indirectly influence immune programming in both pregnancy and the postnatal period. The intrauterine microclimate is critical for maternal and foetal immunological tolerance to sustain viable pregnancy, but appears susceptible to environmental conditions. Targeting aspects of the modern environment that promote aberrant patterns of immune response is logical for interventions aimed at primary prevention of allergic disease. Defining the mechanisms that underpin both natural and therapeutic acquisition of immunological tolerance in childhood will provide insights into the drivers of persistent immune dysregulation. In this review we summarise evidence that allergy is a consequence of intrauterine and early life immune dysregulation, with specific focus on contributing environmental risk factors occurring preconception, in utero and in the early postnatal period. We explore the immunological mechanisms which underpin tolerance and persistence of allergic disease during childhood. It is likely that future investigations within these two domains will ultimately provide a road map for the primary prevention of allergic disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Clinical & Experimental Allergy 03/2015; 45(5). DOI:10.1111/cea.12531 · 4.32 Impact Factor