Human β-defensin-1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra-amniotic infection

Abstract

Problem: Human β-defensins (HBDs) are antimicrobial peptides that participate in the soluble innate immune mechanisms against infection. Herein, we determined whether HBD-1 was present in amniotic fluid during normal pregnancy and whether its concentrations change with intra-amniotic inflammation and/or infection.

Method of study: Amniotic fluid was collected from 219 women in the following groups: (a) midtrimester who delivered at term (n = 35); (b) term with (n = 33) or without (n = 17) labor; (c) preterm labor with intact membranes who delivered at term (n = 29) or who delivered preterm with (n = 19) and without (n = 29) intra-amniotic inflammation and infection or with intra-amniotic inflammation but without infection (n = 21); and (d) preterm prelabor rupture of membranes (pPROM) with (n = 19) and without (n = 17) intra-amniotic inflammation/infection. Amniotic fluid HBD-1 concentrations were determined using a sensitive and specific ELISA kit.

Results: (a) HBD-1 was detectable in all amniotic fluid samples; (b) amniotic fluid concentrations of HBD-1 were changed with gestational age (midtrimester vs term no labor), being higher in midtrimester; (c) amniotic fluid concentrations of HBD-1 were similar between women with and without spontaneous labor at term; (d) among patients with spontaneous preterm labor, amniotic fluid concentrations of HBD-1 in women with intra-amniotic inflammation/infection and in those with intra-amniotic inflammation without infection were greater than in women without intra-amniotic inflammation or infection who delivered preterm or at term; and (e) the presence of intra-amniotic inflammation and infection in patients with pPROM did not change amniotic fluid concentrations of HBD-1.

Conclusion: HBD-1 is a physiological constituent of amniotic fluid that is increased in midtrimester during normal pregnancy and in the presence of culturable microorganisms in the amniotic cavity. These findings provide insight into the soluble host defense mechanisms against intra-amniotic infection.

Keywords: acute chorioamnionitis; cytokines; danger signals; fetal immunity; funisitis; innate immunity; microbial invasion of the amniotic cavity; neutrophils; preterm PROM; sterile intra-amniotic inflammation.

Figure 1.

Amniotic fluid concentrations of human β-defensin-1 (HBD-1) in normal pregnancy. The median concentration of amniotic fluid HBD-1 in midtrimester (n=35) was significantly higher than that of women at term without labor (n=17) [midtrimester: median 13.73 (IQR 6.87–20.44 ng/mL) vs. term no labor: median 9.07 ng/mL (IQR 6.93–12.15 ng/mL); p=0.03]. IQR = interquartile range.

Figure 2.

Amniotic fluid concentrations of human β-defensin-1 (HBD-1) at term pregnancy. There was no difference between the median amniotic fluid concentration of HBD-1 between women with (n=33) and without labor (n=17) at term [term no labor: median 9.07 ng/mL (IQR 6.93–12.15 ng/mL) vs. term labor: median 6.44 ng/mL (IQR 3.59–11.45 ng/mL); p=0.1]. IQR = interquartile range.

Figure 3.

Amniotic fluid concentrations of human β-defensin-1 (HBD-1) in spontaneous preterm labor with intact membranes. The median amniotic fluid concentration of HBD-1 in women with preterm labor and intra-amniotic inflammation and infection who delivered preterm (n=19) was significantly higher than that of women with preterm labor who delivered at term (n=29) [preterm labor with intra-amniotic inflammation and infection who delivered preterm: median 24.36 ng/mL (IQR 17.34–38.91) vs. preterm labor who delivered at term: median 10.87 ng/mL (IQR 8.82–13.94 ng/mL); p<0.001] and women with preterm labor without intra-amniotic inflammation or infection who delivered preterm (n=29) [preterm labor with intra-amniotic inflammation and infection who delivered preterm: median 24.36 ng/mL (IQR 17.34–38.91) vs. preterm labor without intra-amniotic inflammation or infection who delivered preterm: median 12.2 ng/mL (IQR 8.02–18.58 ng/mL); p=0.006]. The median amniotic fluid concentration of HBD-1 in women with preterm labor and intra-amniotic inflammation but without infection who delivered preterm (n=21) was elevated compared to that of women with preterm labor who delivered at term [preterm labor with intra-amniotic inflammation but without infection who delivered preterm: median 18.31 ng/mL (IQR 12.17–32.15 ng/mL) vs. preterm labor who delivered at term: median 10.87 ng/mL (IQR 8.82–13.94 ng/mL); p=0.003] and women with preterm labor without intra-amniotic inflammation or infection who delivered preterm [preterm labor with intra-amniotic inflammation but without infection who delivered preterm: median 18.31 ng/mL (IQR 12.17–32.15 ng/mL) vs. preterm labor without intra-amniotic inflammation or infection who delivered preterm: median 12.2 ng/mL (IQR 8.02–18.58 ng/mL); p=0.02]. IQR = interquartile range. P-values were adjusted for multiple comparisons.

Figure 4.

Amniotic fluid concentrations of human β-defensin-1 (HBD-1) in preterm prelabor rupture of membranes (pPROM). The median amniotic fluid concentrations of HBD-1 were similar between women with pPROM and intra-amniotic inflammation and infection (n=19) and those without intra-amniotic inflammation or infection (n=17) [pPROM with intra-amniotic inflammation and infection: median 15.47 (IQR 8.68–19.51) vs. pPROM without intra-amniotic inflammation or infection: median 12.4 (IQR 9.46–14.77); p=0.2]. IQR = interquartile range.