19: Increased concentration of 17-alpha hydroxyprogesterone caproate correlates with IL-10 to reduce spontaneous preterm birth

Abstract

17-alpha hydroxyprogesterone caproate (17-OHPC) 250 mg reduces recurrent spontaneous preterm birth in women by 33%. We have previously demonstrated that women with the lowest quartile of plasma concentrations of 17- OHPC have elevated rates of preterm birth compared with women in the 2-4th quartiles. The mechanism of action of 17-OHPC is unknown but immune modulation is a possibility. We have previously reported elevated cytokines in the cervical fluid of women with a prior preterm birth. Additionally, circulating cytokines of immunoinhibitory IL-10 and pro-inflammatory TNF alpha have correlated with spontaneous preterm birth. This study sought to determine the relationship between the concentration of 17-OHPC and serum cytokines to determine if efficacy of 17-OHPC correlates with altered immunity. This was an ancillary study analyzing laboratory results from the placebo controlled, randomized trial of omega-3 supplementation and reduction of recurrent preterm birth. Peripheral blood mononuclear cells were isolated from paired blood samples drawn at 16-22 weeks gestation (baseline) and 25-28 weeks gestation (post treatment). IL-10 and TNF-alpha levels were measured with and without stimulation by lipopolysaccharide by ELISA. All women received 17-OHPC in this trial. 17-OHPC concentrations were determined from a single blood sample obtained between 25-28 weeks. Baseline and post-treatment cytokine levels were compared with 17-OHPC serum concentrations in women with and without preterm birth. We compared serum cytokines in women with 17OHPC levels in the first quartile to women in quartiles 2-4. There was a statistically significant increase in LPS stimulated concentrations of IL-10 in women with quartiles 2-4 compared the first quartile (p<0.0001). No differences were seen prior to treatment. There was no statistically significant differences in post treatment TNF-alpha levels. After 17-OHPC administration, there appears to be a concentration relationship between 17-OHPC and LPS stimulated IL-10, an immunoinhibitory cytokine. As has been demonstrated by Harper et al 2013, IL-10 levels correlate with preterm birth. This finding supports an immunomodulatory mechanism of 17-OHPC to prevent recurrent preterm birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)