Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin

British Journal of Clinical Pharmacology - Tập 64 Số 4 - Trang 517-526 - 2007
Caroline M. Forrest1, Gillian Mackay1, Nicholas Stoy1, Trevor W. Stone1, L. Gail Darlington1
1Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow and Epsom General Hospital, Epsom, UK

Tóm tắt

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.AimSince 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.MethodsA 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.ResultsAn 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.ConclusionA 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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Thông tin xuất bản

British Journal of Clinical Pharmacology

Tập 64 Số 4

517-526

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