Melatonin was found to demonstrate potential as an adjunctive therapy for systemic lupus erythematosus and lupus nephritis through its antioxidant and anti-inflammatory properties, according to a narrative review published in the journal Current Molecular Pharmacology.
In the review, Hosseinzadeh et al examined melatonin's mechanisms and clinical evidence in systemic lupus erythematosus management.
A randomized, double-blind, placebo-controlled trial found that melatonin supplementation reduced serum malondialdehyde levels in patients with systemic lupus erythematosus compared with placebo, accompanied by enhanced antioxidant activity. The study enrolled 32 patients who received standard treatment plus either 10 mg of melatonin nightly or a placebo for 12 weeks. Similar benefits were observed in patients with rheumatoid arthritis who received 6 mg of melatonin daily for 12 weeks, demonstrating decreased serum malondialdehyde levels compared with placebo.
Studies showed that patients with systemic lupus erythematosus exhibit lower serum melatonin levels compared with healthy controls. In female patients, decreased melatonin levels appeared to inversely correlate with disease activity. Serum melatonin concentration has therefore emerged as a diagnostic and prognostic indicator; however, no correlation was found between melatonin levels and inflammatory cytokine concentrations.
Genetic studies identified the MTNR1B rs10830963 polymorphism as being associated with increased systemic lupus erythematosus prevalence, and single-nucleotide polymorphisms within the AANAT gene with increased genetic vulnerability to systemic lupus erythematosus.
Melatonin exerts immunomodulatory effects by influencing T helper cell development, inhibiting nuclear factor-κB activation, and reducing inflammatory cytokine synthesis, the researchers explained. The molecule has been found to amplify T-regulatory cell populations and mitigate B-cell activating factor overexpression in cells from patients with systemic lupus erythematosus.
In pristane-induced lupus nephritis mouse models, melatonin administration at a dose of 10 mg/kg/day for 6 months seemed to reduce renal damage and restore normal kidney structure. Melatonin appeared to attenuate transforming growth factor-β1 and interleukin-6 (IL-6) expression, reducing interstitial fibrosis and tubular apoptosis. The treatment was also found to reverse glomerular sclerosis, tubular damage, and mesangial expansion.
Lupus nephritis has emerged as a frequent systemic lupus erythematosus complication, according to the researchers, ranging from asymptomatic mild proteinuria to severe urinary complications with rapid progression toward hypertension and renal failure. Melatonin administration in animal models was seen to mitigate IL-6 elevation, hindering lupus nephritis progression through effects on B-cell–associated autoantibody regulation.
"Administration of melatonin has shown potential in significantly reducing renal damage caused by SLE [systemic lupus erythematosus] by modulating the expression of specific proteins associated with fibrosis, apoptosis, oxidative stress, and inflammation," the researchers wrote. "Considering the high prevalence of renal involvement in SLE, these findings hold significant clinical relevance."
The researchers acknowledged variability in melatonin levels may reflect circadian timing of sample collection, disease activity stages, and methodological differences across studies. Further research is needed to determine optimal dosing regimens, assess long-term effects, and evaluate efficacy as adjunctive therapy, they remarked.
Azam Hosseinzadeh, PhD; Farnoosh Seirafianpour, MD; Mohammad Sheibani, MD, PhD; Ali Jamshidi Naeini, MD; and Saeed Mehrzadi, PhD, all of Iran University of Medical Sciences, Tehran; and Russel J. Reiter, PhD, of UT Health San Antonio, Long School of Medicine, are the corresponding authors of the article in Current Molecular Pharmacology.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.
Source: Current Molecular Pharmacology