Melatonin reduces inflammatory response in peripheral T helper lymphocytes from relapsing‐remitting multiple sclerosis patients

Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the immune system plays a central role. In particular, effector populations such as T helper (Th) 1, Th9, Th17, and Th22 cells are involved in disease development, whereas T regulatory cells (Tregs) are associated with the resolution of the disease. Melatonin levels are impaired in patients with MS, and exogenous melatonin ameliorates the disease in MS animal models by modulating the Th1/Th17/Treg responses and also improves quality of life and several symptoms in patients with MS. However, no study has examined melatonin's effect on T cells from relapsing-remitting MS (RR-MS) patients. Therefore, the objectives of the present study were to evaluate the effects of the in vitro administration of melatonin to peripheral blood mononuclear cells (PBMCs) from 64 RR-MS patients and 64 sex- and age-matched healthy subjects on Th1, Th9, Th17, Th22, and Treg responses and to analyze the expression of the melatonin effector/receptor system in these cells. Melatonin decreased Th1 and Th22 responses in patients, whereas it did not affect the Th17 and Treg subsets. Melatonin also promoted skewing toward a more protective cytokine microenvironment, as shown by an increased anti-inflammatory/Th1 ratio. Furthermore, for the first time, we describe the overexpression of the melatonin effector/receptor system in PBMCs from patients with MS; this alteration might be relevant to the disease because acetylserotonin O-methyltransferase expression significantly correlates with disease progression and T effector/regulatory responses in patients. Therefore, our data suggest that melatonin may be an effective treatment for MS.

Serotonin decreases the production of Th1/Th17 cytokines and elevates the frequency of regulatory CD4+ T‐cell subsets in multiple sclerosis patients

“…Melatonin has a potent anti‐oxidant, anti‐inflammatory, and neuroprotective action , and lower levels of this hormone have been documented in MS patients . In EAE, exogenous melatonin reduced the severity of disease . In MS patients, a study by Alvarez‐Sanchez et al.…”

Melatonin and inflammation—Story of a double‐edged blade

“…Additionally, a reduction of the Th1 response was observed, whereas conclusions concerning a Th17 response did not find their expression in humans . In PHA‐stimulated PBMCs from patients with a remitting type of MS, melatonin decreased the Th1 (release of IL‐2, IL‐12, IFNγ, TNFα) and Th22 responses (IL‐22 release), whereas the Th17 response remained uneffected . In an animal model of autoimmune encephalomyelitis, melatonin elevated IFNγ levels, increased lymphocyte infiltration and astrocyte activation .…”

“…For instance, murine autoimmune encephalomyelitis used as a model for multiple sclerosis (MS) demonstrated upregulation of IL‐10 by melatonin and reduced mononuclear infiltration . Additionally, a reduction of the Th1 response was observed, whereas conclusions concerning a Th17 response did not find their expression in humans . In PHA‐stimulated PBMCs from patients with a remitting type of MS, melatonin decreased the Th1 (release of IL‐2, IL‐12, IFNγ, TNFα) and Th22 responses (IL‐22 release), whereas the Th17 response remained uneffected .…”

Responses of Transgenic Melatonin-Enriched Goats on LPS Stimulation and the Proteogenomic Profiles of Their PBMCs

“…In the past, many studies have investigated the effects of MT on the exacerbated inflammatory response in different animal models [53,54,55]. In the majority of the studies, the MT was exogenously administered [56,57,58].…”