In our earlier work, we found that intrauterine (i.u.) and intraperitoneal (i.p.) injection of LPS (10-µg serotype 0111:B4) induced preterm labor (PTL) with high pup mortality, marked systemic inflammatory response and hypotension. Here, we used both i.u. and i.p. LPS models in pregnant wild-type (wt) and CCR2 knockout (CCR2–/–) mice on E16 to investigate the role played by the CCL2/CCR2 system in the response to LPS.

Basally, lower numbers of monocytes and macrophages and higher numbers of neutrophils were found in the myometrium, placenta, and blood of CCR2–/– vs. wt mice. After i.u. LPS, parturition occurred at 14 h in both groups of mice. At 7 h post-injection, 70% of wt pups were dead vs. 10% of CCR2–/– pups, but at delivery 100% of wt and 90% of CCR2–/– pups were dead. Myometrial and placental monocytes and macrophages were generally lower in CCR2–/– mice, but this was less consistent in the circulation, lung, and liver. At 7 h post-LPS, myometrial ERK activation was greater and JNK and p65 lower and the mRNA levels of chemokines were higher and of inflammatory cytokines lower in CCR2–/– vs. wt mice. Pup brain and placental inflammation were similar. Using the IP LPS model, we found that all measures of arterial pressure increased in CCR2–/– but declined in wt mice.

These data suggest that the CCL2/CCR2 system plays a critical role in the cardiovascular response to LPS and contributes to pup death but does not influence the onset of inflammation-induced PTL.

Summary Sentence

This study used mouse models of preterm labour and sepsis to show that during pregnancy the CCL2/CCR2 system is important in the cardiovascular response to sepsis but while it delays pup death it does not delay LPS-induced preterm labour.