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 -
