A role for the novel cytokine RANTES in pregnancy and parturition

OBJECTIVE: RANTES (regulated on activation, normal T cell expressed and sec reted), a potent and versatile chemokine, is capable of attracting monocyte s, lymphocytes, basophils, and eosinophils. This cytokine has been implicat ed in the regulation of the inflammatory response and in the recruitment of macrophages to the implantation site in early pregnancy. RANTES messenger ribonucleic acid and protein have been detected in fetal tissue and first-t rimester trophoblast in response to bacterial endotoxin. The purpose of thi s study was to determine whether intrauterine infection, parturition (prete rm and term), and gestational age affect the amniotic fluid concentrations of RANTES in human pregnancy. STUDY DESIGN: A cross-sectional study was designed to examine the relations hip between labor, microbial invasion of the amniotic cavity, gestational a ge, and RANTES expression in amniotic fluid. Amniotic fluid was obtained fr om 214 women in the following groups: (1) midtrimester (n = 22), (2) preter m labor with intact membranes in the presence (n = 20) or absence (n = 74) of microbial invasion of the amniotic cavity, (3) term, not in labor (n = 4 4) and term, in labor in the presence (n = 27) and absence (n = 27) of micr obial invasion of the amniotic cavity. Microbial invasion of the amniotic c avity was defined as a positive amniotic fluid culture for microorganisms. RANTES concentrations were determined by use of a sensitive and specific im munoassay. RESULTS: (1) Amniotic fluid RANTES concentrations decrease with advancing g estational age (r = 0.43; P < .01). (2) Labor at term was associated with a n increase in median concentrations of RANTES (labor-median, 8.4 pg/mL; ran ge, <1.3-94.4 vs no labor-median, <1.3 pg/mL; range, <1.3-230.3; P < .01). (3) Women with preterm labor who delivered preterm (no microbial invasion o f the amniotic cavity) had a higher median concentration of amniotic fluid RANTES than those who delivered at term (median, 12.7 pg/mL; range, <1.3-92 8 vs median, <1.3 pg/mL; range, <1.3-127.5; P < .001). (4) Microbial invasi on of the amniotic cavity was associated with a significant increase in med ian amniotic fluid RANTES in both preterm and term labor (preterm labor wit h microbial invasion of the amniotic cavity-median, 51.6 pg/mL; range, <1.3 -2290 vs preterm labor without microbial invasion of the amniotic cavity-me dian, 12.7 pg/mL; range, <1.3-928 and vs preterm labor with delivery at ter m-median, <1.3 pg/mL; range, <1.3-127.5; P < .001 for each; term labor with microbial invasion of the amniotic cavity-median, 16.8 pg/mL; range, <1.3- 171.4 vs term labor without microbial invasion of the amniotic cavity-media n, 8.4 pg/mL; range, <1.3-94.4; P < .05 and vs no labor and no microbial in vasion of the amniotic cavity-median, 1.4 pg/mL; range, <1.3-230.3; P < .00 1 and P < .05, respectively). CONCLUSION: These results support a role for RANTES in the mechanisms of hu man parturition and in the regulation of the host response to intrauterine infection.