A study published in Scientific Reports examined whether melatonin can reduce inflammation in human fetal membranes exposed to a bacterial toxin, focusing on a key immune signaling pathway.
Methods
Fetal membranes were collected from 12 healthy women who underwent uncomplicated term cesarean deliveries without prior labor. Women with diabetes, hypertension, obesity, metabolic diseases, or urinary/vaginal infections in the third trimester were excluded.
Tissues were cultured in a two-chambered system preserving the choriodecidual and amniotic compartments. Before exposure to lipopolysaccharide (LPS), compartments were treated with 1 nM melatonin (a physiological concentration found in amniotic fluid) for 24 hours, with fresh melatonin added every 6 hours due to its short half-life. Inflammation was induced by adding 500 ng/mL LPS to the choriodecidual side. Some samples were co-treated with luzindole, a non-selective melatonin receptor antagonist.
Results
- Cytokines: LPS increased secretion of TNF-α, IL-1β, IL-6, and IL-10. Melatonin significantly reduced all four cytokines, with pronounced reductions in TNF-α and IL-1β. Luzindole diminished these effects, suggesting melatonin receptor mediation.
Melatonin significantly reduced all four inflammatory cytokines tested, with pronounced reductions in TNF-α and IL-1β.
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mRNA Expression: LPS increased TNF-α and IL-1β mRNA, which was suppressed by melatonin and restored by luzindole. Melatonin did not significantly affect IL-6 mRNA.
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Chemokines: LPS increased CCL5, CCL2, and CCL3. Melatonin decreased CCL5 and CCL3 secretion in a compartment-dependent manner but did not affect CCL2. No significant changes in chemokine mRNA were observed.
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Signaling Pathway: LPS increased TLR4, MyD88, and NF-κB protein levels. Melatonin reduced these proteins, and luzindole largely reversed the changes.
Conclusions
Melatonin exerts anti-inflammatory effects in human fetal membranes exposed to LPS-induced inflammation by reducing cytokine secretion, selected chemokines, and modulating the TLR4/MyD88/NF-κB pathway. These effects are partially mediated through melatonin receptors.
The study provides a foundation for future research on targeting melatonin pathways to prevent inflammation-related preterm birth. As an ex vivo study using term, non-labor membranes, it does not demonstrate that melatonin supplementation prevents preterm birth in pregnant patients.