Photoimmunomodulation and melatonin
12 Feb 2010-Journal of Photochemistry and Photobiology B-biology (Elsevier)-Vol. 98, Iss: 2, pp 107-117
TL;DR: Melatonin--one of the universally accepted chronobiotic molecule secreted by the pineal gland is now emerging as one of the most effective immunostimulatory compound in rodents and as oncostatic molecule at least in human.
Abstract: The seasons, and daily physical rhythms can have a profound effect on the physiology of the living organism, which includes immune status. The immune system can be influenced by a variety of signals and one of them is photic stimulus. Light may regulate the immunity through the neuroendocrine system leading to the most recent branch of research the “Photoimmunomodulation”. Mammals perceive visible light (400–700 nm) through some specialized photoreceptors located in retina like retinal ganglion cells (RGC). This photic signal is then delivered to the visual cortex from there to the suprachiasmatic nucleus (SCN) of the hypothalamic region. Melatonin – one of the universally accepted chronobiotic molecule secreted by the pineal gland is now emerging as one of the most effective immunostimulatory compound in rodents and as oncostatic molecule at least in human. Its synthesis decreases with light activation along with norepinephrine and acetylcholine. The changes in level of melatonin may lead to alterations (stimulatory/inhibitory) in immune system. The evidences for the presence of melatonin receptor subtypes on lymphoid tissues heralded the research area about mechanism of action for melatonin. Further, melatonin receptor subtypes-MT1 and MT2 was noted on pars tuberalis, SCN and on lymphatic tissues suggesting a direct action of melatonin in modulation of immunity by photoperiod as well. The nuclear receptors (ROR, RZR etc.) of melatonin are known for its free radical scavenging actions and might be indirectly controlling the immune function.
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TL;DR: Day length provides a virtually noise free environmental signal to monitor and accurately predict time of the year and is the fulcrum mediating redistribution of energetic investment among physiological processes to maximize fitness and survival.
159 citations
Cites background from "Photoimmunomodulation and melatonin..."
...of visual function in the retina [10,91], immunomodulation [131], and cerebrovascular physiology (reviewed in [74])....
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University of Aberdeen1, University of Vienna2, University of Glasgow3, Ohio State University4, University of Nottingham5, Durham University6, Natural Environment Research Council7, University of Oxford8, Max Planck Society9, University of Tromsø10, College of William & Mary11, Tel Aviv University12, University of Delhi13, University of Edinburgh14, University of Michigan15, University of Western Australia16, University of Massachusetts Medical School17, University of Würzburg18, University of Leicester19, Nagoya University20
TL;DR: In this paper, a review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact.
Abstract: The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.
127 citations
TL;DR: Poor sleep efficiency is common in children with AD and can be predicted by the Scoring Atopic Dermatitis index, and lower nocturnal melatonin secretion was significantly associated with sleep disturbance in the patients with AD.
Abstract: Background and objectives Sleep disturbance is common in patients with atopic dermatitis (AD). However, studies have largely been questionnaire-based, and the pathophysiology remains unclear. The aims of this study were to determine objective characteristics of sleep disturbance in children with AD and explore contributing factors and clinical predictors. Methods Sleep parameters were measured by actigraphy and polysomnography in 72 patients with AD and 32 controls ages 1 to 18 years. Urinary 6-sulfatoxymelatonin levels, serum cytokines, and total and allergen-specific immunoglobulin E (IgE) levels were also measured. Results The patients with AD had significantly reduced sleep efficiency, longer sleep onset latency, more sleep fragmentation, and less nonrapid eye movement sleep. Results from actigraphy correlated well with those from polysomnography. The AD disease severity was associated with sleep disturbance (r = 0.55-0.7), and a Scoring Atopic Dermatitis index of ≥48.7 predicted poor sleep efficiency with a sensitivity of 83.3% and a specificity of 75% (area under the curve = 0.81, P = .001). Lower nocturnal melatonin secretion was significantly associated with sleep disturbance in the patients with AD. Other correlates of sleep disturbance included pruritus, scratching movements, higher total serum IgE levels, and allergic sensitization to dust mite and staphylococcal enterotoxins. Conclusions Poor sleep efficiency is common in children with AD and can be predicted by the Scoring Atopic Dermatitis index. Melatonin and IgE might play a role in the sleep disturbance. Further studies are required to explore the mechanisms and clinical implications, and actigraphy could serve as a useful evaluating tool.
120 citations
TL;DR: Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD.
Abstract: Importance Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD. Objective To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD. Design, Setting, and Participants This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these (79%) completed the cross-over period of the trial. Final follow-up occurred on April 13, 2013, and data were analyzed from January 27 to April 25, 2014. Analyses were based on intention to treat. Interventions Melatonin, 3 mg/d, or placebo for 4 weeks followed by a 2-week washout period and then crossover to the alternate treatment for 4 weeks. Main Outcomes and Measures The primary outcome was AD severity evaluated using the Scoring Atopic Dermatitis (SCORAD) index, with scores ranging from 0 to 103 and greater scores indicating worse symptoms. Secondary outcomes included sleep variables measured by actigraphy, subjective change in sleep and dermatitis, sleep variables measured by polysomnography, nocturnal urinary levels of 6-sulfatoxymelatonin, and serum IgE levels. Results After melatonin treatment among the 48 children included in the study, the SCORAD index decreased by 9.1 compared with after placebo (95% CI, −13.7 to −4.6; P P = .02). The improvement in the SCORAD index did not correlate significantly with the change in sleep-onset latency ( r = −0.04; P = .85). No patient withdrew owing to adverse events, and no adverse event was reported throughout the study. Conclusions and Relevance Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD. Trial Registration clinicaltrials.gov Identifier:NCT01638234
105 citations
TL;DR: How the immune-pineal axis concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms is discussed and it is hoped it opens new horizons for the research of side effects of melatonin-based therapies.
Abstract: Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-κB activation in pinealocytes and immune competent cells. Therefore, pathogen- or danger-associated molecular patterns transiently switch the synthesis of melatonin from pinealocytes to immune competent cells, and as the response progresses melatonin inhibition of NF-κB activity leads these cells to a more quiescent state. The opposite effect of NF-κB in pinealocytes and immune competent cells is due to different NF-κB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-κB is called the immune-pineal axis. Finally, we discuss how this concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms and hope it opens new horizons for the research of side effects of melatonin-based therapies.
104 citations
References
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TL;DR: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses.
Abstract: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses. Defining the cellular and molecular mechanisms of helper-T-cell differentiation should lead to rational strategies for manipulating immune responses for prophylaxis and therapy.
4,578 citations
"Photoimmunomodulation and melatonin..." refers background in this paper
...The observation that UV-mediated tolerance and transfer of suppression can be inhibited by neutralizing anti-IL-10 antibodies suggests that the release of IL-10 by UV-induced Tr plays an important role in photoimmunosuppression [41]....
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...In addition, they secrete IL-10 upon hapten-specific stimulation [38–41]....
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...The Th1 population produces IL-2, lymphotoxin and IFN-c, whereas the Th2 cells produce IL-4, IL-5, IL-6 and IL-10 [31]....
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...Some cytokines are predominantly inhibitory for example, IL-10 and IL13 inhibit inflammatory cytokine production by macrophages [5]....
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...Th2 cells secrete IL-4, IL-5, IL-6, and IL-10, which stimulate antibody production by B cells....
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01 Jan 2001
4,346 citations
TL;DR: It is shown that chronic activation of both human and murine CD4+T cells in the presence of interleukin (IL)-10 gives rise to CD4-T-cell clones with low proliferative capacity, producing high levels ofIL-10, low levels of IL-2 and no IL-4.
Abstract: Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such active suppression. Here we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RB(high) splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.
3,782 citations
Book•
01 Sep 1994
TL;DR: Introductory immunology textbook for medical students, advanced undergraduates, and graduate students.
Abstract: Introductory immunology textbook for medical students, advanced undergraduates, and graduate students.
3,751 citations
"Photoimmunomodulation and melatonin..." refers background in this paper
...cytokines are predominantly inhibitory for example, IL-10 and IL13 inhibit inflammatory cytokine production by macrophages [5]....
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...with representative chemokines are C–C chemokines (RANTES, MCP-1, MIP-1a, and MIP-1b), C–X–C chemokines (IL-8), C chemokines (lymphotactin), and CXXXC chemokines (fractalkine) [5]....
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TL;DR: It is shown that retinal ganglion cells innervating the SCN are intrinsically photosensitive, and depolarized in response to light even when all synaptic input from rods and cones was blocked.
Abstract: Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
3,052 citations
"Photoimmunomodulation and melatonin..." refers background in this paper
...intrinsically photosensitive [48] and proposed to act as circadian photoreceptors....
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