A recent ex vivo study published in Scientific Reports reveals that melatonin may reduce infection-triggered inflammation in human fetal membranes, potentially informing future strategies against inflammation-related preterm birth, according to a Jun. 28 report.
Researchers evaluated whether melatonin could decrease lipopolysaccharide-induced inflammation in human fetal membranes and examined the involvement of the TLR4/MyD88/NF-κB signaling pathway. The study involved tissue samples from 12 healthy women who had uncomplicated term cesarean deliveries without prior labor or metabolic diseases. These samples were cultured using a two-chambered system to preserve the separation between maternal-facing and fetal-facing regions, with each side treated independently.
Melatonin was administered at physiological concentrations before exposure to lipopolysaccharide (LPS), a bacterial endotoxin used to simulate infection-driven inflammation. Some tissue samples were also co-treated with luzindole, a non-selective melatonin receptor antagonist, to determine if the observed effects depended on melatonin receptors. Researchers analyzed cytokine and chemokine levels using ELISA assays and measured gene expression via quantitative polymerase chain reaction.
The results showed that LPS exposure triggered significant inflammatory responses in both regions of the fetal membrane by increasing pro-inflammatory cytokines TNF-α, IL-1β, IL-6, as well as anti-inflammatory IL-10. Melatonin treatment significantly reduced secretion of all four cytokines—especially TNF-α and IL-1β—suggesting attenuation of early inflammatory signals. When tissues were treated with luzindole, many anti-inflammatory effects of melatonin diminished, indicating these actions are at least partly mediated through melatonin receptors.
Additional findings indicated that LPS increased chemokines CCL5, CCL2, and CCL3; however, melatonin decreased production of CCL5 and CCL3 but did not significantly affect CCL2 levels or transcriptional expression for these chemokines. Further analysis showed that LPS increased TLR4, MyD88, and NF-κB proteins involved in inflammatory signaling pathways; these increases were reduced by melatonin but reversed when luzindole was present.
The researchers concluded that while their ex vivo findings support a potential role for targeting melatonin-related pathways to limit infection-associated membrane inflammation—and thus possibly reduce risk factors for preterm birth—further studies are needed before clinical recommendations can be made.
