A review of the multiple actions of melatonin on the immune system

  title={A review of the multiple actions of melatonin on the immune system},
  author={Antonio Carrillo-Vico and Juan Miguel Guerrero and Patricia Judith Lardone and Russel Joseph Reiter},
This review summarizes the numerous observations published in recent years which have shown that one of the most significant of melatonin’s pleiotropic effects is the regulation of the immune system. The overview summarizes the immune effects of pinealectomy and the association between rhythmic melatonin production and adjustments in the immune system as markers of melatonin’s immunomodulatory actions. The effects of both in vivo and in vitro melatonin administration on non-specific, humoral… 
The role of melatonin in the cells of the innate immunity: a review
The effects and action mechanisms of melatonin in the different cells that belong to or participate in the innate immunity, such as monocytes–macrophages, dendritic cells, neutrophils, eosinophils, mast cells, and natural killer cells are summarized.
Multiple Facets of Melatonin in Immunity: Clinical Applications
Overall, melatonin acts as an immune activator in basal or immunodepressed conditions, whereas it might exert a negative regulation under transient or chronic exacerbated immune response.
The modulatory role of melatonin on immune responsiveness.
The immunomodulatory role of melatonin, with regard to infection, inflammation and autoimmunity, is outlined here, and the evidence discussed in this review strengthens the notion that the nature of an immune response may be modified, and therefore therapeutically manipulated, by circadian effector signals.
Melatonin: a pleiotropic molecule regulating inflammation.
Influence of Melatonin on the Immune System of Fish: A Review
It is suggested that melatonin represents an important component of fish endocrine-immune system interactions, and the elucidation of the defense mechanisms of fish will facilitate the development of health management tools to support the growing finfish aquaculture industry and address questions concerning the origins and evolution of the immune system in vertebrates.
A review of the molecular aspects of melatonin’s anti‐inflammatory actions: recent insights and new perspectives
This review summarizes recent research data focusing on the modulation of the expression of different inflammatory mediators by melatonin and the effects on cell signaling pathways responsible for the indole’s anti‐inflammatory activity.
Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases
The role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease are summarized and highlighted.
Melatonin: Buffering the Immune System
The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation.
Distribution, function and physiological role of melatonin in the lower gut.
The presently available information on melatonin effects in the lower gut is summarized and available in vitro and in vivo data are discussed to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower Gut.


The effect of melatonin on cellular activation processes in human blood
Melatonin may have a beneficial effect by suppressing the expression of TF activity in LPS‐stimulated monocytes of whole blood, which may be physiologically important in upregulation of the immune system.
Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism.
It is reported that exogenous melatonin counteracts completely the effect of acute anxiety-restraint stress on thymus weight and antibody response to sheep red blood cells (SRBC) and suggests that melatonin exerts its remarkable anti-stress effect on antigen-activated cells via an opiatergic mechanism.
Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism.
Findings point to a fundamental immunoregulatory role of circadian melatonin and to an activity of the neurohormone via opioid peptides.
Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system.
It is shown that human lymphocyte-synthesized melatonin plays a crucial role modulating IL-2/IL-2 receptor system because when blocking melatonin biosynthesis by the tryptophan hydroxylase inhibitor, parachlorophenylalanine, both IL- 2 and IL-1 receptor levels fell, restoring them by adding exogenous melatonin.
Melatonin affects proopiomelanocortin gene expression in the immune organs of the rat.
It has been demonstrated for the first time that melatonin can act on the level of proopiomelanocortin (POMC) gene expression and establishes that the formation of short POMC transcripts in the bone marrow and lymph nodes may be upregulated by melatonin.
Melatonin counteracts the inhibitory effect of PGE2 on IL‐2 production in human lymphocytes via its mt1 membrane receptor
Prostaglandin E2 (PGE2), a potent inflammatory mediator, inhibits IL‐2 production in human lymphocytes by a cyclic AMP (cAMP)‐dependent mechanism and is postulate, for the first time, a physiological role of the mt1 melatonin membrane receptor in the human immune system.
Is there a role for melatonin in supportive care?
  • P. Lissoni
  • Medicine, Biology
    Supportive Care in Cancer
  • 2002
The present clinical results demonstrate that the pineal hormone MLT may be successfully administered in medical oncology in the supportive care of untreatable advanced cancer patients and for the prevention of chemotherapy-induced toxicity.
Intracellular second messengers involved in melatonin signal transduction in chicken splenocytes in vitro
It is demonstrated that the stimulatory and inhibitory effect of melatonin on chicken splenocytes in vitro, dependent on the magnitude of cell stimulation, resulted from two different subtypes of membrane receptors.