Role of Melatonin in Viral, Bacterial and Parasitic Infections.

In all mammals, the circulating pool of MLTs is synthesized in the pineal gland during the night's darkness hours. Its main function is synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm or circulate, and plays a detoxifying and cytoprotective role.

'Distant socializing,' not 'social distancing' as a public health strategy for COVID-19.

Social distancing, also referred to as physical distancing, means creating a safe distance of at least two meters (six feet) between yourself and others. This is a term popularized during the COVID-19 pandemic, as it is one of the most important measures to prevent the spread of this virus. However, the term 'social distancing' can be misleading, as it may imply that individuals should stop socializing.

Adrenergic Modulation of Hematopoiesis.

Hematopoiesis produce every day billions of blood cells and takes place in the bone marrow (BM) by the proliferation and differentiation of hematopoietic stem cells (HSC). HSC are found mainly adjacent to the BM vascular sinusoids where endothelial cells and mesenchimal stromal cells promote HSC maintenance by producing a variety of factors. Other cell types that regulate HSC niches include sympathetic nerves, non-myelinating Schwann cells and a variety of mature hematopoietic cells such as macrophages, neutrophils, and megakaryocytes.

Sympathoadrenergic modulation of hematopoiesis: a review of available evidence and of therapeutic perspectives.

Innervation of the bone marrow (BM) has been described more than one century ago, however the first in vivo evidence that sympathoadrenergic fibers have a role in hematopoiesis dates back to less than 25 years ago. Evidence has since increased showing that adrenergic nerves in the BM release noradrenaline and possibly also dopamine, which act on adrenoceptors and dopaminergic receptors (DR) expressed on hematopoietic cells and affect cell survival, proliferation, migration and engraftment ability. Remarkably, dysregulation of adrenergic fibers to the BM is associated with hematopoietic disturbances and myeloproliferative disease.

Pinealectomy affects bone mineral density and structure--an experimental study in sheep.

Background: Osteoporosis and associated fractures are a major public health burden and there is great need for a large animal model. Melatonin, the hormone of the pineal gland, has been shown to influence bone metabolism. This study aims to evaluate whether absence of melatonin due to pinealectomy affects the bone mass, structure and remodeling in an ovine animal model.

β2-Adrenergic agonists bias TLR-2 and NOD2 activated dendritic cells towards inducing an IL-17 immune response.

This study tested the hypothesis that activation of β2-adrenoceptors on DCs influences NOD2 signaling along with its cross-talk with Toll-like receptor-2 resulting in altered Th cell priming ability. Th17 cells are a newly discovered lineage of CD4(+) T cells involved in defense against extracellular bacteria and also implicated in autoimmune disorders. Initiation and polarization of the adaptive immune response is controlled by innate immune recognition mediated by DCs.

Immunomodulation by melatonin: its significance for seasonally occurring diseases.

Melatonin is not only synthesized by the pineal gland but also in many other organs and tissues of the body, particularly by lymphoid organs such as the bone marrow, thymus and lymphocytes. Melatonin participates in various functions of the body, among which its immunomodulatory role has assumed considerable significance in recent years. Melatonin has been shown to be involved in the regulation of both cellular and humoral immunity.

Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways.

Melatonin, an endogenous signal of darkness, is an important component of the body's internal time-keeping system. As such it regulates major physiological processes including the sleep wake cycle, pubertal development and seasonal adaptation. In addition to its relevant antioxidant activity, melatonin exerts many of its physiological actions by interacting with membrane MT1 and MT2 receptors and intracellular proteins such as quinone reductase 2, calmodulin, calreticulin and tubulin.

Adrenergic modulation of dendritic cell cancer vaccine in a mouse model: role of dendritic cell maturation.

The aim of the present study was to evaluate the role of beta2-adrenergic receptors (beta2-ARs) in the outcome of a dendritic cell (DC)-based cancer vaccine in the murine E.G7-ovalbumin (OVA) model. We found that unlike the beta2-AR expressed on antigen loaded DCs, beta2-ARs expressed in the site of DCs inoculation may influence the efficacy of the antitumor response.

Sympathetic nervous modulation of the skin innate and adaptive immune response to peptidoglycan but not lipopolysaccharide: involvement of beta-adrenoceptors and relevance in inflammatory diseases.

Disorders of the skin immune activity are implicated in the pathogenesis of acquired inflammatory skin disorders. Inflammatory diseases including psoriasis, atopic dermatitis, lichen planus and vitiligo have also been associated with local alterations of adrenergic mechanisms and emotional stress. Here we show that the beta-adrenergic receptors antagonist propranolol along with peptidoglycan, but not LPS, combined with intradermal injection of a soluble protein, shifted the recall memory response to the Th1 type.

Melatonin, environmental light, and breast cancer.

Although many factors have been suggested as causes for breast cancer, the increased incidence of the disease seen in women working in night shifts led to the hypothesis that the suppression of melatonin by light or melatonin deficiency plays a major role in cancer development. Studies on the 7,12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea experimental models of human breast cancer indicate that melatonin is effective in reducing cancer development. In vitro studies in MCF-7 human breast cancer cell line have shown that melatonin exerts its anticarcinogenic actions through a variety of mechanisms, and that it is most effective in estrogen receptor (ER) alpha-positive breast cancer cells.

Circadian rhythms: glucocorticoids and arthritis.

Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time-dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time-dependent inflammatory reaction with effects opposite those of cortisol.

Sympathetic nervous system influence on the innate immune response.

Our studies focused on the sympathetic nervous system (SNS) influence on dendritic cells (DCs), which play a crucial role in the innate immune response. We found that DCs express a variety of adrenergic receptors (ARs) with alpha1-ARs playing a stimulatory and beta2-ARs an inhibitory effect on DCs migration. beta2-ARs in skin and bone marrow-derived DCs when stimulated by bacterial toll-like receptors (TLRs) agonists respond to norepinephrine (NE) by decreased interleukin-12 (IL-12) and increased IL-10 production which in turn downregulates inflammatory cytokine production and CCR7 expression and thus their migration ability leading to reduced T helper-1 (Th1) priming.

Melatonin: Nature's most versatile biological signal?

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'.

The role of melatonin in immuno-enhancement: potential application in cancer.

Melatonin, a neurohormone produced mainly by the pineal gland, is a modulator of haemopoiesis and of immune cell production and function, both in vivo and in vitro. Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines, and its administration favours Th1 priming. In both normal and leukaemic mice, melatonin administration results in quantitative and functional enhancement of natural killer (NK) cells, whose role is to mediate defenses against virus-infected and cancer cells.

Melatonin, immune function and aging.

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age.

Adrenergic modulation of dendritic cells function: relevance for the immune homeostasis.

Dendritic cells (DC) play a key role in determining the appropriate immune response to invading pathogens and tolerance to self antigens. Here I review the evidence that dendritic cell functions may be tuned by the sympathetic nervous system via the local release of norepinephrine. In the presence of antigens or microbial products, such as agonists for Toll-like receptors 2 and 4, norepinephrine inhibits dendritic cell migration, antigen presentation and T-helper cells type 1 priming.

Role of melatonin in neurodegenerative diseases.

The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains.

Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison.

Background: Altered functioning of the hypothalamic-pituitary-adrenal axis and altered melatonin production might modulate the circadian symptoms in patients with rheumatoid arthritis.

Objective: To investigate the influence of different winter photoperiods on the circadian rhythms of serum melatonin, cortisol, tumour necrosis factor alpha (TNFalpha), and interleukin 6 (IL6) in patients with rheumatoid arthritis from a north Europe country (Estonia) and a south Europe country (Italy).

Methods: The patients from Estonia (n = 19) and Italy (n = 7) had similar disease severity and duration and were compared with healthy age and sex matched controls in the two countries.

Does melatonin play a disease-promoting role in rheumatoid arthritis?

The pineal neurohormone melatonin (MLT) has been widely shown to exert an immunostimulatory and antiapoptotic role, mainly by acting on Th cells and on T and B cell precursors, respectively. Thus, MLT might favor or promote autoimmune diseases by acting directly on immature and mature immunocompetent cells. In fact, preclinical and clinical evidence point to a disease-promoting role of MLT in rheumatoid arthritis (RA).

The endogenous cannabinoid 2-arachidonoyl glycerol as in vivo chemoattractant for dendritic cells and adjuvant for Th1 response to a soluble protein.

The decision-making mechanisms that determine the choice of the appropriate effector immune response to a microbial challenge are poorly understood. The endocannabinoid 2-arachidonoylglycerol (2-AG), injected intradermally in mice together with a soluble protein and a T helper-2 (Th2) priming Toll-like receptors (TLRs) agonist during primary immunization, shifts the memory response to the Th1 type. This effect can be shown by the enhanced hypersensitivity response and by the Th1 pattern of cytokines production that was abolished by the specific cannabinoid receptor CB2 antagonist SR 144528.