Ti trovi in Relazioni Congressi | IS IL6 OVERPRODUCTION THE MISSING LINK AMONG SLEEP DISORDERS,DIABESITY,AGING AND AGING RELATED DISEASES?---Congresso Internaz.Medicina Antiaging-Rigenerativa-PARIGI--OTTOBRE 2011--
IS IL6 OVERPRODUCTION THE MISSING LINK AMONG SLEEP DISORDERS,DIABESITY,AGING AND AGING RELATED DISEASES?---Congresso Internaz.Medicina Antiaging-Rigenerativa-PARIGI--OTTOBRE 2011--
IS IL6 OVERPRODUCTION THE MISSING LINK AMONG SLEEP DISORDERS,DIABESITY,AGING AND AGING RELATED DISEASES?
Sleep plays a vital role in our health and well being like that exerted by nutrition,stress controll ,physical activity etc. and we know today that the quality of sleep is related to the quality and expectancy of life.
Sleep exerts different functions,the most important are: energy conservation, the consolidation of memory,hormonal and immune systems regulation and body-mind restoration.
The immune system benefits from the effects of sleep that regulates the circadian alternance between cell-mediated immunity(TH1 immune branch), which develops mostly at night (first part of sleeping time under the influence of SWS) and that is promoted by hormones such as melatonin and growth hormone and the humoral immunity(TH2 immune branch) that is expressed during the final part of sleeping time and during daylight hours and that is stimulated by cortisol and vit.D. On the other hand, sleep is influenced by immune system, pro-inflammatory cytokines play somnogenic effects while anti-inflammatory cytokines promote wake up altering sleep.Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune, hematopoietic,hormonal and metabolic activities and its potent ability to induce the acute phase response.
IL-6 that is one of the main drivers of TH17 immune branch, concomitantly regulates proinflammatory and antiinflammatory activities and contributes to both the development and the resolution of the acute inflammatory response. IL-6 is a cytokine that is produced by the cells of immune system, vascular endothelial cells, adipocytes and skeletal muscle and has shown to have anti-inflammatory as well as pro-inflammatory properties.Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Chron disease,Castleman’s disease, psoriasis, post-menopausal osteoporosis.IL6 overproduction is supposed to be involved also in the pathogenesis of aging process and aging related diseases like diabesity,cardiovascular diseases(CVD),dementia,sarcopenia,frailty,disability,cancer,
autoimmune diseases etc. However, a fundamental question remains of whether elevated levels of IL-6 are aimed at resolving an inflammatory response that is inappropriately long or whether a primary dysregulation of IL-6 production is responsible for a chronic proinflammatory state,which has a negative impact on health status.It is possible that in some diseases aging and chronic inflammation related,like sarcopenia,osteopenia,autoimmune diseases and cancer,IL6 could exert a pathogenetic role;in other disorders il 6 could be the effect of the diseases rather than a causative factor(obesity,diabetes,metabolic syndrome),while in others it could exert a double role of cause and effect at the same time (cvd,dementia). Future studies that evaluate the effects of blocking the IL-6 signaling in older persons affected by a chronic proinflammatory state and different patterns of comorbidity may shed light on this question.
In both young and older persons, the secretion of IL-6 follows a circadian rhythm with two nadirs at about 8.00 a.m. and 9.00 p.m., and two zeniths at about 7 p.m.00 and 5.00 a.m.REM sleep enhances IL 6 production through catecolamines’s action,IL6 is inhibited by deep sleep(3-4 NON REM sleep) and by wake time (through the action of cortisol).For this reason, it’s is produced mainly in the second part of night when REM SLEEP is more expressed and is more inhibited during the first part of day (under cortisol influence).On the other hand,IL6 influences negatively deep sleep and rem sleep (in the first part of the night) while promotes sleep induction and enhances superficial sleep (1-2 non rem sleep), REM sleep (in the second part of night) and cortisol release.
Sleep disorders that are very common in the population, such as chronic insomnia, restless legs syndrome,obstructive apnea may promote aging,are cofactors of many age-related diseases and increase the risk of mortality for various causes.Among the diseases promoted by insomnia and by other sleep disorders,are reported obesity, diabetes, cardiovascular disease and metabolic syndrome.Sleep disturbances that characterize the aging process would also be an important cofactor of cognitive disorders of varios degree, of immunosenescence and inflammaging.Several studies have proved that chronic insomnia can promote an increased risk of mortality for cardiovascular diseases (women especially).
Sleep disorders promotes aging and aging related dIseases generating a global psyconeuroendocrineimmune imbalancement.
Inflammaging or low grade chronic inflammation is one of the main player of this imbalancement that binds sleep disorders to aging process and aging related diseases. While acute inflammations normally tightly controlled and is a part of the healing process, the low-grade elevation of inflammatory markers seen in older adults has been associated with a number of chronic conditions of aging, such as cardiovascular disease, diabetes,obesity,sarcopenia, physical disability, cognitive decline,cancer and increased mortality.A number of inflammatory markers, especially Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) have the most consistent associations with age-related chronic diseases and disability.Their production increases with age and in particular high il6’s blood level checked at 8 a.m.(> 4,18 pg/ml) is considered an important marker of unsuccessfull aging and aging related deseases.The exact mechanism for the increase of inflammatory cytokines with age has not been fully understood.Proposed mechanisms include the known increase in total and visceral adiposity with age(fat mass produces about the 15%-30% of il6), the declining levels of sex hormones and igf1 after menopause and andropause,disnutrition,physical inactivity,suclinical chronic infection(CMV),dysbiosis,chronic stress and chronic pain diseases.Oxidative damage with aging,which further invokes an inflammatory response, may be another mechanism leading to an increase in the level of these markers.The physiologic alteration of sleep architecture that characterizes aging process and sleep disorders aging related,are also considered an importat pathogenetic factor of inflammaging.
An interesting study published on Biol.Psychiatry(2008), has proved that sperimental sleep loss activates tnf gene expression through an increased adrenergic output related to stress.Tnf alpha is a strong activator of nfkb and then of il6 and inflammatory cascade.An enhancement of il6 release is also promoted by the activation of adrenergic tone.NF-κB activation is thought to contribute to the pathophysiology of diseases such as diabetes mellitus, cardiovascular disease,cancer and atherosclerosis. Given evidence that sleep disturbance is associated with each of these medical disorders , sleep dependent NF-κB activation may be a common mechanism in the cumulative burden that finally leads to morbidity and mortality. An other study published by the same university (UCLA) in the 2010,showed that sleep loss promotes an higher activation of inflammatory cascade in women than in men. Whereas both females and males showed a marked increase in the lipopolysaccharide (LPS) stimulated production of IL-6 and TNF-α in the morning immediately after sleep deprivation, production of these cytokines during the early and late evening was increased in the females as compared to decreases in the males.These results have implications for understanding the role of sleep disturbance in the differential risk profile for inflammatory disorders between the sexes and the increased cardiovascular mortality rate in women with sleep loss than in men (women suffer of sleep disorders and of chronic inflammatory deseases more than men).To conclude we can say that, old age is associated with decreased sex steroid concentrations, increased proportional body fat, decreased quantity and quality of sleep, and frequent chronic pain/inflammatory conditions that promote inflammaging.Reducing the secretion of IL-6 in elderly, by administration of sex steroids, decreasing fat through diet and exercise, improving night time sleep, and controlling adequately chronic pain and inflammation, may improve sleep, daytime alertness, and performance (altered by accumulation of evening cortisol and daytime IL6 during aging) and decrease the risk of common ailments of old age, e.g. metabolic and cardiovascular problems, cognitive disorders, and osteoporosis.