Excisional treatment for cervical intraepithelial neoplasia (CIN) increases the risk of preterm birth (PTB) in a subsequent pregnancy. Treatment may disturb the innate immune system, which includes the production of natural antimicrobial peptides by the cervical epithelium. Human Beta Defensin-1 (hBD-1) has potent antiviral, as well as antibacterial activity, and Secretory Leucocyte Protease Inhibitor (SLPI) is found at high levels in the mucus plug of a healthy pregnancy. We examined the effect of antimicrobial peptides in response to excisional treatment.
Levels of hBD-1 and SLPI were determined in cervicovaginal secretions using enzyme-linked immunosorbent assay (ELISA) and normalized to total protein content.
Two-hundred and seventy nine women with CIN and normal controls were sampled. Mean AMP ratios were lowest in healthy controls, rising with increasing disease severity (hBD-1: normal 4962pg/ml vs high-grade CIN 7173pg/ml (p=0.038); SLPI: normal 806422pg/ml vs high-grade CIN 850075pg/ml (p=0.123).
Eighty women were sampled 6 months following excision treatment. Levels of hBD-1 were significantly lower compared to pre-treatment (9073pg/ml vs 3838pg/ml, p<0.0001) and were also lower than healthy, untreated controls (p=0.0143). SLPI levels also decreased in the same manner (137800pg/ml vs 99270pg/ml), but this was not statistically significant.
Excisional treatment leads to a reduction in the levels of antimicrobial peptides, which serve as a first-line defense against pathogens. Treated women may therefore be more susceptible to ascending infections in pregnancy, known to be a significant cause of PTB.