Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin.

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)-1beta, IL-6, tumour necrosis factor (TNF)-alpha], 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-1beta, IL-6 and TNF-alpha. 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.