CXCL6 (granulocyte chemotactic protein-2): a novel chemokine involved in the innate immune response of the amniotic cavity

Problem: CXCL6 is a potent pro-inflammatory neutrophil chemoattractant and activator whose activity during pregnancy is not well-established. The purpose of this study was to determine if CXCL6 is present in amniotic fluid (AF) and if CXCL6 concentrations in AF change with labor (pre-term and term) or intra-amniotic Infection/inflammation (IAI).

Method of study: A cross-sectional study was designed including the following groups: (1) mid-trimester (n = 65); (2) term no labor (n = 20); (3) term labor (n = 44); (4) patients with pre-term labor (PTL) with subsequent term delivery (n = 57); (5) PTL without IAI who delivered pre-term (n = 47); and (6) PTL with IAI (n = 62). AF CXCL6 concentrations were determined by ELISA.

Results: CXCL6 was present in all term samples, but undetectable in 64/65 mid-trimester specimens. Patients with PTL and IAI had a significantly higher median AF CXCL6 concentration than those with PTL without IAI [228.9 pg/mL (0.0-8344.8) versus 55.7 pg/mL (0-454.4); P < 0.05] and those with PTL and term delivery [41.5 pg/mL (0-279.0); P < 0.05]. The median AF CXCL6 concentration did not change with spontaneous term labor [term no labor: 81.1 pg/mL (8.5-201.7) versus term labor: 75.2 pg/mL (6.7-378.7): P = 0.7].

Conclusion: (1) CXCL6 is detectable in AF and its concentration increases with gestational age; (2) IAI results in increased AF CXCL6 concentrations, suggesting that CXCL6 plays a role in the deployment of an inflammatory response; (3) In contrast to related chemokines, specifically IL-8, AF CXCL6 does not appear to be involved in spontaneous term parturition. These observations are novel, and suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity.