Effects of melatonin on plasma levels of TNF-α, IL-1 and IL-6 in mice after lipopolysaccharide administration

Bitzer-Quintero, Oscar Kurt; Ortíz, Genaro Gabriel; Ruiz-Rizo, L.; Torres-Mendoza, Blanca Miriam; Vázquez-Valls, Eduardo; Rodríguez-Pérez, Miguel Alberto

doi:10.1080/09291010400028948

Cited by 8 publications

(4 citation statements)

References 36 publications

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“…There is a further paradox in that, despite the decrease of tissue peroxidation and the rise in ESR and neopterin concentrations, there are no significant differences between placebo and melatonin groups either in the assessments of patients' symptoms, or in the concentrations of the proinflammatory cytokines IL‐1β, IL‐6 or TNF‐α. There is a substantial volume of work favouring the view that melatonin can suppress the production of TNF‐α[9, 18, 19, 41–44]. However, many of these studies have use different doses or concentrations, different cell types in vitro including monocytes, Th‐2 lymphocytes, macrophages or undefined cellular sources, or various in vivo systems, and different activating stimuli such as lipopolysaccharide or phytohaemagglutinin, which make it difficult to compare with the present study.…”

Section: Discussionmentioning

confidence: 99%

“…However, many of these studies have use different doses or concentrations, different cell types in vitro including monocytes, Th‐2 lymphocytes, macrophages or undefined cellular sources, or various in vivo systems, and different activating stimuli such as lipopolysaccharide or phytohaemagglutinin, which make it difficult to compare with the present study. Some of these same investigations have also noted increased production of IL‐1β at doses or concentrations that suppressed TNF‐α[19], while other studies have observed that melatonin has little or no effect on the release of either IL‐1β or TNF‐α, especially from macrophages [45, 46]. In contrast, there is good evidence that there are receptors for melatonin on synovial macrophages [47, 48] which promote the release of some Th‐1‐type proinflammatory cytokines such as IL‐12 [49].…”

Section: Discussionmentioning

confidence: 99%

“…Melatonin exhibits several additional anti‐inflammatory actions, such as reduction of the translocation of nuclear factor‐κB, and has been reported to inhibit the production of proinflammatory cytokines [9, 18, 19]. It may also possess the ability to modulate cell interactions by affecting factors such as adhesion molecules that could be relevant to the progression of diseases such as arthritis [14].…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin

Forrest

Mackay

Stoy

et al. 2007

Brit J Clinical Pharma

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What is already known about this subject • There is good evidence that oxidative stress, associated with the generation of free radicals, is a major contributor to joint damage in rheumatoid arthritis. • It is also well established that melatonin is one of the most powerful, endogenous free radical scavengers, and it is very safe for human use. • We have therefore examined whether melatonin might be a useful adjunctive compound with which to treat arthritis. What this study adds • Once‐nightly administration of melatonin increases concentrations of some inflammatory markers, but patients experience no significant improvement in symptoms and no changes of proinflammatory cytokine concentrations. • Melatonin is an effective antioxidant, but because it is either not sufficiently effective, or it has some proinflammatory activity, it is not likely to prove beneficial in patients. Aim Since melatonin is antioxidant and has some anti‐inflammatory actions, we have tested it as adjunctive treatment in patients with rheumatoid arthritis, to determine whether it can improve patients' symptoms. Methods A total of 75 patients were allocated randomly to receive melatonin 10 mg at night in addition to ongoing medication, or a placebo of identical appearance. Monthly blood samples were taken and disease severity assessed over 6 months, plasma being analysed for inflammatory indicators [C‐reactive protein, erythrocyte sedimentation rate (ESR), neopterin], proinflammatory cytokines [interleukin (IL)‐1β, IL‐6, tumour necrosis factor (TNF)‐α], lipid peroxidation products and the kynurenine pathway metabolites of tryptophan. Results An increase of ESR (two‐way anova F(1,127) = 5.24, P = 0.024) and neopterin concentrations (F(1,136) = 4.64, P = 0.033) was observed in treated patients compared with controls, reflected also in a significant trend for both to decline in placebo‐treated patients (P = 0.022), but not the melatonin‐treated group. Peroxidation products showed a significant trend to decrease in placebo‐ but not melatonin‐treated patients. These results suggest a proinflammatory action, but there were no significant effects of melatonin treatment on clinical assessments of patient symptoms or the concentrations of three proinflammatory cytokines, IL‐1β, IL‐6 and TNF‐α. Melatonin significantly increased plasma kynurenine concentrations (F(1,124) = 4.24, P = 0.041), again suggesting proinflammatory activity. Conclusion A daily dose of 10 mg melatonin shows a slowly developing antioxidant profile in patients with arthritis and increases the concentrations of some inflammatory indicators, but these effects are not associated with any change of proinflammatory cytokine concentrations or clinical symptoms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin

Forrest

Mackay

Stoy

et al. 2007

Brit J Clinical Pharma

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“…At this regard, it has been reported that natural antioxidants such as melatonin [23], quercetin [24], luteolin [25] and other antio xidants (butylated hydroxyanisole, tetrahydropapaveroline,nordihydroguiauretic acid, 10, 11-dihydro xyaporphine) [25] are potent inhibitors of the LPS-induced production of TNF-α production in vivo.…”

Section: Discussionmentioning

confidence: 99%

Renovato¹,

Davalos²,

Tirado³

et al. 2012

AJB

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Lipopolysaccharide, a main co mponent of Gram-negative bacterial endotoxin is the lead ing cause of sepsis or endotoxic shock. This condition generates tissue hypoperfusion and leads to a state of acute metabolic-circulatory dysfunction and multio rgan systemic failure wh ich contributes to amplify the inflammatory response and resulting in the release of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6). The effect of NutriSim© on serum pro-inflammatory cytokine concentrations were investigated in lipopolysaccharide-treated male W istar rats. Animals were rando mized into five groups: control groups receiv ing a single intraperitoneal in jection of physiologic saline solution or NutriSim© (10µl), respectively; LPS (20 mg/Kg, i.p.); NutriSim© treat ment 15 min before o r after LPS in the same aforementioned dose. The results showed that a single dose of NutriSim© prio r or before the endotoxic insult diminishes significantly the production of serum TNF-α, IL-1 and IL-6. Therefore NutriSim© can modulate an inflammatory response in experimental model of endotoxic shock.

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Immune Stimulation by Exogenous Melatonin During Experimental Endotoxemia

Effenberger-Neidnicht

Brencher

Broecker-Preuß

et al. 2014

Inflammation

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Melatonin has been shown to enhance the immune response under immune-compromised conditions. However, its immune-modulatory effects under inflammatory conditions are unclear at present. Both pro- and anti-inflammation has been reported. To study time-dependent effects of melatonin on the general immune response during endotoxemia in more detail, we used two models in male rats: per-acute endotoxemia was induced by lipopolysaccharide (LPS) bolus injection (2.5 mg/kg), sub-acute endotoxemia by LPS infusion (2.5 mg/kg × h). Melatonin was applied directly before and 2 h after LPS administration (3 mg/kg, each). The LPS-induced formation of the pro-inflammatory cytokines tumor necrosis factor alpha, interferon-gamma, interleukin (IL)-1α/β, IL-5, and IL-6 and of the anti-inflammatory cytokine IL-10 was further amplified by melatonin, although it was only significant during per-acute endotoxemia. In both models, melatonin had no effect on the LPS-induced nitric oxide release. These findings show that exogenous melatonin is capable of enhancing the general immune response under inflammatory conditions.

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Effects of melatonin on plasma levels of TNF-α, IL-1 and IL-6 in mice after lipopolysaccharide administration

Cited by 8 publications

References 36 publications

Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin

Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin

NutriSim© Diminishes an Endotoxin-stimulated Proinflammatory Cytokine Production

Immune Stimulation by Exogenous Melatonin During Experimental Endotoxemia

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