In vivo, cytokines function as part of an elaborate and complex network. Investigating cytokines individually does not provide insight into their holistic function. In this analysis, we considered cytokines in functional clusters. We explored the relative balance of the pro- and anti-inflammatory cervical milieu as related to midtrimester sonographic cervical length among women with a history of spontaneous preterm birth.
In a prospective longitudinal cohort of 48 women with a history of spontaneous preterm birth, women were enrolled between 15 and 0/7 and 23 and 6/7 weeks and had 1-6 visits (median 2). At each visit, transvaginal ultrasound for cervical length and pelvic exam for collection of cervical fluid was performed. IL-1β, IL-6 and IL-8 were selected to represent pro-inflammatory cytokines and IL-4, IL-10, and IL-13 were selected to represent anti-inflammatory cytokines. In order to standardize each cytokine, for each woman, the concentration of each cytokine was divided by its median, yielding a multiple of the median (MoM) value. We summed the 3 pro-inflammatory MoMs to generate the pro-inflammatory score, and did the same for the anti-inflammatory score. The relation between cervical length and cytokine milieu was assessed using Generalized Linear Modeling.
The relative balance of pro-inflammatory to anti-inflammatory score had a significant negative linear association with cervical length (β=-0.04, p=0.03) after adjusting for race, smoking, gonorrhea, chlamydia, and bacterial vaginosis.
Among women with a prior preterm birth, shorter cervical length is associated with a relatively more pro-inflammatory cervical milieu. This novel finding suggests that cervical shortening is not simply anatomic but is also associated with biochemical and immunological changes, suggesting opportunities for future mechanistic and interventional research.
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.