Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Melatonin reduces oxidative stress in surgical neonates. Short- but Not Long-Term Melatonin Administration Reduces Central Levels of Brain-Derived Neurotrophic Factor in Rats with Inflammatory Pain Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model: a randomized, double-blind, placebo-controlled, three-arm crossover study The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial Melatonin Supplementation May Improve the Outcome of Patients with Hemorrhagic Stroke in the Intensive Care Unit Effects of blackcurrant-based juice on atherosclerosis-related biomarkers in cultured macrophages and in human subjects after consumption of a high-energy meal. Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study.
Multiple sclerosis ( MS ) is a chronic inflammatory disease , which leads to focal plaques of demyelination and tissue injury in the central nervous system ( CNS ) . Neuroinflammation and oxidative stress are involved in the pathogenesis of MS , promoting tissue damage and demielinization . Current research findings suggest that melatonin has antioxidant and neuroprotective effects . The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis ( RRMS ) . 36 patients diagnose with RRMS treated with Interferon β-1b ( IFNβ-1b ) were enrolled in a double bind , r and omized , placebo controlled trial . The experimental group received orally 25 mg/d of melatonin for 6 months . After melatonin administration , we observed a significant decrease in serum concentration of pro-inflammatory cytokines and oxidative stress markers ; 18 % for TNF-α ( p < 0.05 ) , 34.8 % for IL-1β ( p < 0.05 ) , 34.7 % for IL-6 ( p < 0.05 ) , 39.9 % for lipoperoxides ( LPO ) ( p < 0.05 ) and 24 % for nitric oxide catabolites ( NOC ) levels ( p < 0.05 ) , compared with placebo group . No significant difference in clinical efficacy outcomes were found between groups . Melatonin treatment was well tolerated and we did not observe significant differences in rates of side effects between the two groups . We concluded that melatonin administration during 6 months period is effective in reducing levels of serum pro-inflammatory cytokines and oxidative stress markers in patients with RRMS . These data support future studies evaluating the safety and effectiveness of melatonin supplementation in RRMS patients BACKGROUND / PURPOSE Cytokines are inflammatory mediators found in the circulation after surgery . Newborns have less protection against oxidation and are very susceptible to free radical oxidative damage . Melatonin has been reported recently to reduce oxidative stress in neonates with sepsis , asphyxia , and respiratory distress . The aim of this study has been to determine if melatonin would lower interleukin (IL)-6 , IL-8 , tumor necrosis factor alpha ( TNF-alpha ) and nitrite/nitrate ( NOx ) levels and modify serum inflammation parameters , improving the clinical course of surgical neonates . METHODS Ten newborns ( group 1 ) , 5 with surgical malformations and respiratory distress ( group 1a ) and 5 with isolated abdominal surgical malformations ( group 1b ) received a total of 10 doses of melatonin ( 10 mg/kg ) at defined times interval for 72 hours . The treatment was started within 3 hours after the end of surgery . Ten surgical neonates ( group 2 ) , did not receive melatonin .  Twenty healthy neonates ( group 3 ) served as control . Blood sample s were collected at the end of operation ; before treatment with the antioxidant ; and 24 hours 72 hours , and 7 days after start of treatment with melatonin or placebo , respectively . RESULTS Postoperative value of cytokines and NOx levels of groups 1 and 2 were significantly higher than group 3 . Compared with group 1b , group 2 displayed significantly higher cytokines and NOx levels at 24 hours , 72 hours , and at 7 days . In group 1a the immediate postoperative values of cytokines were significantly higher than group 1b and group 2 , but a significant improvement was observed after administration of melatonin with significantly lower levels of IL-6 and IL-8 with respect to group 2 . An improvement of clinical outcome was observed by progressive reduction of clinical parameters of inflammation . CONCLUSIONS Melatonin reduces cytokines and NOx levels showing potent antioxidant properties with improvement in clinical outcome . Further studies are warranted to define , on larger numbers , the role of melatonin in surgical patients Objective : To evaluate the effect of short- and long-term administration of melatonin on central brain-derived neurotrophic factor ( BDNF ) levels in rats with acute and chronic inflammatory pain . Methods : The animals were allocated to one of two experiments : experiment 1 or experiment 2 . In experiment 1 , all animals were injected with complete Freund 's adjuvant ( CFA ) to induce inflammation and were r and omly allocated to receiving melatonin ( 60 mg/kg ) or vehicle . Injections were administered 1 h after CFA and once daily for 2 more days ( for a total of 3 days of melatonin administration ) . In experiment 2 , fifteen days after CFA injection , the animals were treated with melatonin ( 50 mg/kg ) or vehicle for 8 days . The animals were killed by decapitation 24 h after the last melatonin or vehicle administration , and an ELISA assay was performed to detect BDNF expression in the spinal cord , brainstem , and prefrontal cortex of the rats in both groups . Data were analyzed using Student 's t test and the results are expressed as means ± SEM . Results : In the first experiment , the BDNF levels of the melatonin group were reduced in the prefrontal cortex ( Student 's t test , p = 0.01 ) and increased in the spinal cord ( Student 's t test , p = 0.04 ) . In experiment 2 , BDNF levels were similar in both groups for all structures ( Student 's t test , p > 0.00 for all ) . A two-way ANOVA reveled a significant effect of structures ( p = 0.0001 ) but not of treatment ( p > 0.05 ) . The prefrontal cortex presented higher BDNF levels than other structures ( ANOVA/Student-Newman-Keuls test , p = 0.0001 ) . Considering the relationship between BDNF levels in all three structures , we found an effect of central nervous system structures ( p = 0.01 ) and an interaction between treatment and structures ( p = 0.04 ) . Conclusion : The high spinal cord BDNF levels and the low prefrontal cortical BDNF levels observed in rats with acute CFA-induced inflammation  following short-term melatonin administration may be related to the pain-modulating and neuroprotective effects of this protein . Long-term melatonin administration did not alter BDNF levels in chronic inflammation Abstract Antinociceptive effects of melatonin have been documented in a wide range of experimental animal models . The aim of this study was to investigate the analgesic , antihyperalgesic , and anti-inflammatory properties of melatonin using a vali date d burn injury ( BI ) model in healthy male volunteers . The design was a r and omized , double-blind , placebo-controlled , three-arm crossover study . Each volunteer participated in 3 identical study sessions with intravenous administration of placebo , melatonin 10 mg , or melatonin 100 mg . Sixty minutes after bolus injection of study medication , a BI was induced by a computerized contact thermode ( 47.0 ° C , 420 seconds , 5.0 × 2.5 cm2 ) . Pain ratings during the BI and quantitative sensory testing at baseline and at 1 , 2 , 4 , and 6 hours after the BI were performed . Quantitative sensory testing included assessment s of secondary hyperalgesia areas , mechanical and thermal thresholds in the BI area , and pressure algometry . Furthermore , markers of inflammation , skin-reflectance spectrophotometry , and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area . Pain during the BI and secondary hyperalgesia areas were defined as primary outcomes . Twenty-nine volunteers were r and omized and completed the study . While the BI induced large secondary hyperalgesia areas and significantly increased the markers of inflammation , no significant effects of melatonin were observed with respect to primary or secondary outcomes , compared with placebo . The administration of melatonin was not associated with any adverse effects . Melatonin did not demonstrate any analgesic , antihyperalgesic , or anti-inflammatory properties in the BI model Background Diabetes mellitus ( DM ) and periodontitis are two common chronic diseases with bidirectional relationship . Oxidative stress plays a key role in the pathogenesis of these two diseases . The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status , serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis ( CP ) . Material s and methods In this double-blind clinical trial study , 50 type 2 DM patients with CP were r and omly allocated to the intervention and control groups . The intervention and control groups received either 6 mg melatonin or placebo ( 2 tablets ) once a day . Serum levels of melatonin , tumor necrosis factor-alpha ( TNF-α ) , interleukin-6 ( IL-6 ) , hs-C-reactive protein ( hs-CRP ) , clinical attachment loss ( CAL ) , pocket depth ( PD ) , bleeding on probing ( BOP ) and plaque index were evaluated in all subjects pre- and post-intervention . Results Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention . The mean changes of melatonin were significantly higher in intervention group compared with control group . IL-6 and hs-CRP levels were significantly ( p = 0.008 and p = 0.017 , respectively ) reduced in the intervention group . The mean changes of IL-6 were significantly lower in the intervention group compared with the control group ( p = 0.04 ) . In the intervention group , PD and CAL were significantly decreased after intervention ( p < 0.001 ) . There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention ( p < 0.001 ) . Conclusions Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP Objective : Although mechanical ventilation is frequently a life-saving therapy , its use can result in unwanted side effects . It has been well documented that the choice of sedating agent may influence the duration of mechanical ventilation .  Melatonin is a sedative and analgesic agent without any respiratory depressant effect which makes it an attractive adjuvant for sedation in the intubated patients . The aim of this study is to evaluate the effect of melatonin on the duration of mechanical ventilation in patients with hemorrhagic stroke . Methods : Forty adult intubated patients with hemorrhagic stroke , who were admitted to the Intensive Care Unit ( ICU ) within 24 h of onset , were enrolled in this r and omized double-blind study . Subjects in the melatonin group received 30 mg of melatonin every night throughout the nasogastric tube .  Length of ICU stay , mortality , and duration of mechanical ventilation were recorded for all patients . Findings : The duration of mechanical ventilation and length of ICU stay were shorter in patients who received melatonin in comparison with the control group , and this difference was statistically significant for the length of ICU stay and marginally significant for the duration of mechanical ventilation . Although not statistically significant , the mortality rate of the control group was 30 % , almost double that of the study group ( 15 % ) . Conclusion : Melatonin possesses hypnotic , analgesic , anti-inflammatory , and anti-oxidative properties that distinguish it as an attractive adjuvant in patients under mechanical ventilation . In conclusion , the administration of melatonin may facilitate the weaning process through decreasing the consumption of sedatives with respiratory depressant properties as well as preventing ventilator-associated lung injury Regular consumption of fruit and vegetables may be associated with decreased CVD risk . In the present study , we investigated the effects of blackcurrant ( BC ) juice , rich in polyphenols and ascorbic acid , on oxidative and inflammatory biomarkers in cultured macrophages in vitro and in human subjects with an atherosclerosis-prone phenotype ( after consumption of a high-energy meal ) . In cultured macrophages ( RAW264.7 ) , BC treatment significantly inhibited lipopolysaccharide-induced inflammation as indicated by lower mRNA levels of TNF-α , IL-1β and inducible NO synthase ( iNOS ) and lower nuclear p65 levels indicating decreased NF-κB activity . iNOS protein levels were lower and haem oxygenase 1 levels higher in BC-treated cells when compared with untreated controls . Subjects given a high-energy meal had elevated serum glucose and insulin levels with no significant difference between the BC-based juice and placebo treatment groups . TAG following meal ingestion tended to be attenuated after the BC treatment . Plasma ascorbic acid and radical-scavenging capacity were decreased following placebo meal consumption ; however , BC significantly elevated both parameters compared with baseline and placebo ingestion . Plasma oxidised LDL , α-tocopherol and paraoxonase activity were unchanged in both treatment groups . Furthermore , production of TNF-α and IL-1β was not significantly changed by BC meal consumption . The present results suggest potential antioxidative and anti-inflammatory properties of BC in vitro in cultured macrophages . Although the observations were not directly transferable to a postpr and ial in vivo situation , the present results show that BC juice consumption may improve postpr and ial antioxidant status as indicated by higher ascorbic acid levels and free radical-scavenging capacity in plasma BACKGROUND Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer 's disease ( AD ) . Omega-3 fatty acids ( ω-3 FAs ) found in fish and fish oil have several biological properties that may be beneficial in AD . However , they may also auto-oxidize and induce in vivo lipid peroxidation . OBJECTIVE The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA . METHODS Forty patients with moderate AD were r and omized to receive 1.7 g DHA ( 22:6 ) and 0.6 g EPA ( 20:5 ) or placebo for 6 months . Urinary sample s were collected before and after supplementation . The levels of the major F2-isoprostane , 8-iso-PGF2α , a consistent in vivo biomarker of oxidative stress , and 15-keto-dihydro-PGF2α , a major metabolite of PGF2α and biomarker of inflammatory response , were measured . RESULTS F2-isoprostane in urine increased in the placebo group after 6 months , but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α . At baseline , the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs , and a positive correlation to linoleic acid . 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid . CONCLUSION The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostagl and in F2α . The correlative relationships to FAs indicate a potential role of FAs in immunoregulation
The results of the present meta- analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators
Inflammatory processes are involved in chronic diseases .
It has been suggested that melatonin reduces inflammation by its radical scavenging properties ; however , the results of the previous studies are inconclusive .
The objective of the present meta- analysis is to determine the direction and magnitude of melatonin supplementation effect on inflammatory biomarkers .