Role of Melatonin in the Regulation of Differentiation of T Cells Producing Interleukin-17 (Th17)

Куклина, Е. М.; Glebezdina, N. S.; Nekrasova, I. V.

doi:10.1007/s10517-016-3242-4

Cited by 24 publications

(26 citation statements)

References 13 publications

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“…Sleep disorders: These needed to be addressed by treating Lyme and associated coinfections, as well as ruling out other causes of sleep related problems (such as OSA, RLS, BPH, depression, anxiety, long acting stimulant and/or caffeine use). Treatment of insomnia using various medications (i.e., trazadone, tiagabine, mirtazapine, cyclobenzaprine, and pregabalin) and herbal therapies which support sleep and the circadian rhythm (i.e., valerian root and melatonin, which also lowers IL-17) were often needed [189]. Chart review indicated that balancing hormones (phosphatidylserine can be used to lower high adrenal function at night) [190] while stimulating GABA receptors (using GABA L-theanine) also were occasionally helpful in getting the patient to sleep.…”

Section: Discussionmentioning

confidence: 99%

Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2

Horowitz¹,

Freeman²

2018

Healthcare

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We present a precision medical perspective to assist in the definition, diagnosis, and management of Post Treatment Lyme Disease Syndrome (PTLDS)/chronic Lyme disease. PTLDS represents a small subset of patients treated for an erythema migrans (EM) rash with persistent or recurrent symptoms and functional decline. The larger population with chronic Lyme disease is less understood and well defined. Multiple Systemic Infectious Disease Syndrome (MSIDS) is a multifactorial model for treating chronic disease(s), which identifies up to 16 overlapping sources of inflammation and their downstream effects. A patient symptom survey and a retrospective chart review of 200 patients was therefore performed on those patients with chronic Lyme disease/PTLDS to identify those variables on the MSIDS model with the greatest potential effect on regaining health. Results indicate that dapsone combination therapy decreased the severity of eight major Lyme symptoms, and multiple sources of inflammation (other infections, immune dysfunction, autoimmunity, food allergies/sensitivities, leaky gut, mineral deficiencies, environmental toxins with detoxification problems, and sleep disorders) along with downstream effects of inflammation may all affect chronic symptomatology. In part two of our observational study and review paper, we postulate that the use of this model can represent an important and needed paradigm shift in the diagnosis and treatment of chronic disease.

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Section: Discussionmentioning

confidence: 99%

Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2

Horowitz¹,

Freeman²

2018

Healthcare

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“…The release of proinflammatory cytokines, such as IL‐1β (in earlier studies, IL‐1), IL‐2, IL‐6, IL‐12, TNFα, and IFNγ in response to melatonin has been repeatedly observed in monocytes, monocyte‐derived cells and T‐helper cells type 1, of IL‐17 in non‐preactivated Th17 cells, and of IL‐1β, TNFα and IFNγ in splenocytes, too . Although most studies clearly point into this direction, deviating findings have also been published.…”

Section: Proinflammatory Actions As Revealed By Studies On Immune Cellsmentioning

confidence: 96%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

344

350

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Melatonin is an immune modulator that displays both pro‐ and anti‐inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte‐derived cell lines, can be assumed to enhance the resistance against pathogens. However, they can be detrimental in autoimmune diseases. Anti‐inflammatory actions are of particular medicinal interest, because they are observed in high‐grade inflammation such as sepsis, ischemia/reperfusion, and brain injury, and also in low‐grade inflammation during aging and in neurodegenerative diseases. The mechanisms contributing to anti‐inflammatory effects are manifold and comprise various pathways of secondary signaling. These include numerous antioxidant effects, downregulation of inducible and inhibition of neuronal NO synthases, downregulation of cyclooxygenase‐2, inhibition of high‐mobility group box‐1 signaling and toll‐like receptor‐4 activation, prevention of inflammasome NLRP3 activation, inhibition of NF‐κB activation and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2). These effects are also reflected by downregulation of proinflammatory and upregulation of anti‐inflammatory cytokines. Proinflammatory actions of amyloid‐β peptides are reduced by enhancing α‐secretase and inhibition of β‐ and γ‐secretases. A particular role in melatonin's actions seems to be associated with the upregulation of sirtuin‐1 (SIRT1), which shares various effects known from melatonin and additionally interferes with the signaling by the mechanistic target of rapamycin (mTOR) and Notch, and reduces the expression of the proinflammatory lncRNA‐CCL2. The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

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“…Notably, these findings can be seen in the context of pro-oxidant and cytotoxic effects exerted by melatonin in monocytes, as observed above an activation threshold as low as 50 pM [55]. Moreover, melatonin was found to increase another proinflammatory cytokine, IL-17A, in Th17 cells [56], an effect that spreads proinflammatory responses by inducing the release of other mediators, such as IL-1β, IL-6, TNFα, the neutrophil-attracting Il-8, and by upregulating cyclooxygenase-2 (COX-2) and iNOS (inducible NO synthase) [57,58,59,60,61,62,63,64,65]. This host of secondary effects by IL-17A has been shown to be involved in autoimmune diseases and in neuroinflammation and is, therefore, of relevance to age-related health problems and to adverse effects of melatonin, especially in autoimmunity.…”

Section: Melatonin and The Proinflammatory Networkmentioning

confidence: 99%

Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks

Hardeland

2019

IJMS

248

187

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Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes in the immune system, a deteriorating circadian system, and reductions in sirtuin-1 (SIRT1) activity. In non-tumor cells, several effects of melatonin are abolished by inhibiting SIRT1, indicating mediation by SIRT1. Melatonin is, in addition to its circadian and antioxidant roles, an immune stimulatory agent. However, it can act as either a pro- or anti-inflammatory regulator in a context-dependent way. Melatonin can stimulate the release of proinflammatory cytokines and other mediators, but also, under different conditions, it can suppress inflammation-promoting processes such as NO release, activation of cyclooxygenase-2, inflammasome NLRP3, gasdermin D, toll-like receptor-4 and mTOR signaling, and cytokine release by SASP (senescence-associated secretory phenotype), and amyloid-β toxicity. It also activates processes in an anti-inflammatory network, in which SIRT1 activation, upregulation of Nrf2 and downregulation of NF-κB, and release of the anti-inflammatory cytokines IL-4 and IL-10 are involved. A perhaps crucial action may be the promotion of macrophage or microglia polarization in favor of the anti-inflammatory phenotype M2. In addition, many factors of the pro- and anti-inflammatory networks are subject to regulation by microRNAs that either target mRNAs of the respective factors or upregulate them by targeting mRNAs of their inhibitor proteins.

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Role of Melatonin in the Regulation of Differentiation of T Cells Producing Interleukin-17 (Th17)

Cited by 24 publications

References 13 publications

Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2

Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2

Melatonin and inflammation—Story of a double‐edged blade

Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks

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