The link between the epidemics of obesity and allergic diseases: does obesity induce decreased immune tolerance?

TY - JOUR

T1 - The link between the epidemics of obesity and allergic diseases

T2 - does obesity induce decreased immune tolerance?

AU - Hersoug, Lars-Georg

AU - Linneberg, A

PY - 2007/10

Y1 - 2007/10

N2 - There is increasing epidemiological evidence that obesity increases the risk of asthma, atopic, and autoimmune diseases. We hypothesize that the increase in these diseases is caused, at least in part, by decreased immunological tolerance as a consequence of immunological changes induced by adipokines (e.g. leptin and adiponectin) and cytokines [e.g. interleukin 6 (IL6) and tumor necrosis factor alpha (TNFalpha)] secreted by white adipose tissue. The increasing body weight increases the levels of circulating IL6, leptin, and TNFalpha. IL6 and leptin down-regulate the activity of regulatory T-lymphocytes (Tregs). Additionally, adiponectin, which decreases with increasing obesity, down-regulates the secretion of IL10 from macrophages and adipocytes. These changes in IL6, leptin, and IL10 decrease the regulatory effect of Tregs resulting in decreased immunological tolerance to antigens. In pregnant women, these obesity-induced immunological changes might be transmitted to the fetus by epigenetic inheritance thereby increasing the risk of atopic disease. We propose that obesity results in immunological changes resulting in decreased immunological tolerance to antigens and skewing of the immune system towards a Th2 cytokine profile increasing the risk of allergy and other immune-mediated diseases. Furthermore, this hypothesis offers a unifying explanation for the observation that older siblings appear to confer protection against atopic diseases, preeclampsia, and certain autoimmune diseases. More studies are definitely needed to explore further the immunological effects of obesity and its possible effects on allergic disease.

AB - There is increasing epidemiological evidence that obesity increases the risk of asthma, atopic, and autoimmune diseases. We hypothesize that the increase in these diseases is caused, at least in part, by decreased immunological tolerance as a consequence of immunological changes induced by adipokines (e.g. leptin and adiponectin) and cytokines [e.g. interleukin 6 (IL6) and tumor necrosis factor alpha (TNFalpha)] secreted by white adipose tissue. The increasing body weight increases the levels of circulating IL6, leptin, and TNFalpha. IL6 and leptin down-regulate the activity of regulatory T-lymphocytes (Tregs). Additionally, adiponectin, which decreases with increasing obesity, down-regulates the secretion of IL10 from macrophages and adipocytes. These changes in IL6, leptin, and IL10 decrease the regulatory effect of Tregs resulting in decreased immunological tolerance to antigens. In pregnant women, these obesity-induced immunological changes might be transmitted to the fetus by epigenetic inheritance thereby increasing the risk of atopic disease. We propose that obesity results in immunological changes resulting in decreased immunological tolerance to antigens and skewing of the immune system towards a Th2 cytokine profile increasing the risk of allergy and other immune-mediated diseases. Furthermore, this hypothesis offers a unifying explanation for the observation that older siblings appear to confer protection against atopic diseases, preeclampsia, and certain autoimmune diseases. More studies are definitely needed to explore further the immunological effects of obesity and its possible effects on allergic disease.

KW - Adipose Tissue, White

KW - Asthma

KW - Causality

KW - Comorbidity

KW - Disease Outbreaks

KW - Epigenesis, Genetic

KW - Female

KW - Humans

KW - Hypersensitivity

KW - Immune Tolerance

KW - Intercellular Signaling Peptides and Proteins

KW - Interleukin-10

KW - Interleukin-6

KW - Male

KW - Maternal-Fetal Exchange

KW - Metabolic Networks and Pathways

KW - Obesity

KW - Pregnancy

KW - T-Lymphocytes, Regulatory

KW - Tumor Necrosis Factor-alpha

U2 - 10.1111/j.1398-9995.2007.01506.x

DO - 10.1111/j.1398-9995.2007.01506.x

M3 - Journal article

C2 - 17845592

SN - 0105-4538

VL - 62

SP - 1205

EP - 1213

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

IS - 10

ER -