Direct Effects of Inflammatory Cytokines on Mouse Uterine Contraction

Problem

Uterine contractions signal labor onset, with elevated pro-inflammatory cytokines playing a pivotal role. Prior studies have explored their effects on prostaglandins, oxytocin, and signaling pathways, but have overlooked their direct effects on uterine contractions. Here, we aim to investigate the direct effects of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) on contractions to ascertain if they have immediate observable effects like those reported for lipopolysaccharide (LPS) and other effects.

Method of Study

Tension recordings were used to assess the direct effects of cytokines and/or LPS on mouse uterine contractions. Calcium imaging was employed to observe calcium oscillations in cytokine-pretreated myometrial smooth muscle cells (MSMCs) in response to oxytocin. The release of inflammatory cytokines and chemokines from uterine explants after LPS and/or cytokines application was investigated using Luminex.

Results

IL-1β, IL-6, and TNF-α rapidly enhanced contractions of term pregnant mouse uterus. LPS combined with TNF-α intensified contractions compared to LPS alone, although this effect was not statistically significant in our results (p > 0.050). Pretreatment of MSMCs with IL-1β, IL-6, or TNF-α increased calcium oscillations in response to oxytocin. LPS and/or cytokine significantly stimulated the release of IL-1β, IL-6, TNF-α, Chemokine (C-X-C motif) ligand 1 (CXCL1), and monocyte chemoattractant protein-1 (MCP1) from uterine explants in vitro.

Conclusions

Inflammatory cytokines have short-term and long-term effects on mouse uterine contractions, which together contribute to progressively stronger contractions during labor.