Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis

Sánchez-López, Angélica Lizeth; Ortíz, Genaro Gabriel; Pacheco-Moisés, Fermín Paul; Mireles-Ramírez, Mario Alberto; Bitzer-Quintero, Oscar Kurt; Delgado-Lara, Daniela L.C.; Ramírez-Jirano, Luis Javier; Velázquez-Brizuela, Irma E.

doi:10.1016/j.arcmed.2018.12.004

Cited by 79 publications

(50 citation statements)

References 36 publications

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“…Previous studies by Gitto et al [ 34 ] used melatonin in newborns with respiratory distress with success due to antioxidant and anti-inflammatory effects. In a study of patients with multiple sclerosis, melatonin has been shown to reduce serum concentrations of TNF-α, IL-6, IL-1β, and lipoperoxides, further leading to evidence that it may reduce inflammatory cytokines [ 35 ]. Testing melatonin in ICU patients in the past has not shown significant adverse events.…”

Section: Discussionmentioning

confidence: 99%

Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review

Quirch¹,

Lee²,

Rehman³

2020

J Med Internet Res

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged medicine and health care on a global scale. Its impact and frightening mortality rate are in large part attributable to the fact that there is a lack of available treatments. It has been shown that in patients who are severely ill, SARS-CoV-2 can lead to an inflammatory response known as cytokine storm, which involves activation and release of inflammatory cytokines in a positive feedback loop of pathogen-triggered inflammation. Currently, cytokine storm is one of the leading causes of morbidity and mortality in SARS-CoV-2, but there is no proven treatment to combat this systemic response. Objective The aim of this paper is to study the cytokine storm response in SARS-CoV-2 and to explore the early treatment options for patients who are critically ill with the coronavirus disease (COVID-19) in the early stages of the pandemic by reviewing the literature. Methods A literature review was performed from December 1, 2000, to April 4, 2020, to explore and compare therapies that target cytokine storm among SARS-CoV-2 and prior coronavirus cases. Results A total of 38 eligible studies including 24 systematic reviews, 5 meta-analyses, 5 experimental model studies, 7 cohort studies, and 4 case reports matched the criteria. Conclusions The severity of the cytokine storm, measured by elevated levels of interleukin-1B, interferon-γ, interferon-inducible protein 10, and monocyte chemoattractant protein 1, was associated with COVID-19 disease severity. Many treatment options with different targets have been proposed during the early stages of the COVID-19 pandemic, ranging from targeting the virus itself to managing the systemic inflammation caused by the virus and the excessive cytokine response. Among the different agents to manage cytokine storm in patients with COVID-19, there is developing support for convalescent plasma therapy particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. Treatment options that were proposed in the beginning phases of the pandemic were multidimensional, and further research is needed to develop a more established treatment guideline.

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Section: Discussionmentioning

confidence: 99%

Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review

Quirch¹,

Lee²,

Rehman³

2020

J Med Internet Res

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“…In addition to the documented anti-inflammatory benefits of melatonin, it has a very high safety profile even when used in high doses; there is no evidence that melatonin exaggerates inflammatory responses. In a randomized trial, oral intake of 25 mg/day melatonin for 6 months promoted a significant reduction in serum concentrations of IL-6 and IL-1β [80]. Similarly, in the acute phase of inflammation, including brain reperfusion [81], and coronary artery reperfusion [82], melatonin intake of 6 mg/day and 5 mg/day, respectively, for less than 5 days reduced levels of pro-inflammatory cytokines.…”

Section: Melatonin and Its Safetymentioning

confidence: 95%

Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed

et al. 2020

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The recent pandemic of COVID-19 has already infected millions of individuals and has resulted in the death of hundreds of thousands worldwide. Based on clinical features, pathology, and the pathogenesis of respiratory disorders induced by this and other highly homogenous coronaviruses, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response contribute to COVID-19 pathology; these are caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This leads to a cytokine storm and subsequent progression triggering acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), and often death. We and others have reported melatonin to be an anti-inflammatory and anti-oxidative molecule with a high safety profile. It is effective in critical care patients by reducing their vascular permeability and anxiety, inducing sedation, and improving their quality of sleep. As melatonin shows no harmful adverse effects in humans, it is imperative to introduce this indoleamine into clinical trials where it might be beneficial for better clinical outcomes as an adjuvant treatment of COVID-19-infected patients. Herein, we strongly encourage health care professionals to test the potential of melatonin for targeting the COVID-19 pandemic. This is urgent, since there is no reliable treatment for this devastating disease.

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“…Although there is no report related to the use of melatonin in patients with COVID-19, in subjects with other diseases and a higher level of inflammation, the application of melatonin may show promising results with strong attenuation of circulating cytokine levels. This was documented in patients with diabetes mellitus and periodontitis (51) and severe multiple sclerosis (52). In the acute phase of inflammation, during surgical stress (53), cerebral reperfusion (54) or reperfusion of the coronary artery (55), treatment with melatonin reduced the level of proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

High doses of melatonin as a potential therapeutic tool for the neurologic sequels of covid-19 infection

Cardinali

2020

Melatonin Res.

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The therapeutic potential of melatonin as an agent to counteract the consequences of COVID-19 infections is due to its wide-ranging effects as a powerful antioxidant, anti-inflammatory, and immunostimulant, as well as to a possible antiviral action. In view of the recently reported evidence on the occurrence of neurological sequels in COVID-19-infected patients, another putative application of melatonin emerges based on its neuroprotective properties. In this manuscript a brief discussion of melatonin activity in animal models of ischemic and hemorrhagic stroke and the allometric calculations of the possible human equivalent doses are made. Based on the safety of melatonin, and in order to maximize its therapeutic opportunity, doses of 100 - 300 mg p.o. or i.v. are proposed.

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Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis

Cited by 79 publications

References 36 publications

Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review

Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review

Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed

High doses of melatonin as a potential therapeutic tool for the neurologic sequels of covid-19 infection

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