CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor

Abstract

Problem: To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM).

Method of study: This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay.

Results: (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm.

Conclusion: Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis.

Keywords: allograft; amniocentesis; biomarker; chorioamnionitis; chronic inflammation; cytokine; maternal anti-fetal rejection.

Figure 1

The median concentration of AF CXCL10 in patients according to the presence or absence of acute chorioamnionitis (≥stage 2) or chronic chorioamnionitis. The median (interquartile range: IQR) concentration of AF CXCL10 (ng/mL) was highest in patients with chronic chorioamnionitis. The median (IQR) concentration of AF CXCL10 (ng/mL) was 1.6 (0.9‐3.4), 3.1 (1.1‐6.9), 4.1 (1.9‐7.7), and 3.9 (3.0‐9.7) in patients with neither acute chorioamnionitis nor chronic chorioamnionitis, acute chorioamnionitis (≥stage 2), chronic chorioamnionitis, and acute and chronic chorioamnionitis, respectively. AF, amniotic fluid; CXCL, C‐X‐C motif chemokine; acute chorioamnionitis, the presence of acute chorioamnionitis ≥stage 2 in the absence of chronic chorioamnionitis; chronic chorioamnionitis, the presence of chronic chorioamnionitis in the absence of acute chorioamnionitis ≥stage 2

Figure 2

The median concentration of AF IL‐6 in patients with acute chorioamnionitis ≥stage 2 and/or chronic chorioamnionitis. The median (interquartile range: IQR) AF concentration of IL‐6 (ng/mL) was highest in patients with acute chorioamnionitis ≥stage 2. The median (IQR) AF concentration of IL‐6 (ng/mL) was 1.5 (0.6‐4.2), 41.6 (5.3‐20.7), 1.6 (0.7‐5.4), and 17.6 (3.9‐167.4) in patients with neither acute nor chronic chorioamnionitis, acute chorioamnionitis, chronic chorioamnionitis, or acute and chronic chorioamnionitis, respectively. AF, amniotic fluid; IL, interleukin; acute chorioamnionitis, the presence of acute chorioamnionitis ≥stage 2 in the absence of chronic chorioamnionitis; chronic chorioamnionitis, the presence of chronic chorioamnionitis in the absence of acute chorioamnionitis ≥stage 2; *P value <.05

Figure 3

Magnitudes of association between the study groups according to amniotic fluid IL‐6 and CXCL10 concentrations and the presence or absence of acute (≥stage 2) or chronic chorioamnionitis. Results were obtained by fitting a multinomial logistic regression model and adjusting for gestational age at amniocentesis. AF, amniotic fluid; CXCL, C‐X‐C motif chemokine; IL, interleukin. Normal AF IL‐6 and CXCL10 concentrations: IL‐6 <2.6 ng/mL and CXCL10 <2.2 ng/mL; isolated increase in AF IL‐6 concentration: IL‐6 ≥2.6 ng/mL; isolated increase in AF CXCL10 concentration: CXCL10 ≥2.2 ng/mL; increase in both AF IL‐6 and CXCL10 concentrations: IL‐6 ≥2.6 ng/mL and CXCL10 ≥2.2 ng/mL. Acute chorioamnionitis: the presence of acute chorioamnionitis ≥stage 2 in the absence of chronic chorioamnionitis; chronic chorioamnionitis: the presence of chronic chorioamnionitis in the absence of acute chorioamnionitis ≥stage 2. None of the patients grouped by their normal AF IL‐6 and CXCL10 concentrations had both acute and chronic placental inflammatory lesions; therefore, the computation of the odds ratios relative to the common reference cannot be performed. Red values indicate statistically significant associations between the study group on the left and the outcome named in the column header

Figure 4

Magnitudes of association between the study groups on the left and the outcomes listed in the column heading at the top. Results were obtained by fitting a multinomial logistic regression model and adjusting for gestational age at amniocentesis. AF, amniotic fluid; CXCL, C‐X‐C motif chemokine; IL, interleukin. Normal AF IL‐6 and CXCL10 concentrations: IL‐6 <2.6 ng/mL and CXCL10 <2.2 ng/mL; isolated increase in AF IL‐6 concentration: IL‐6 ≥2.6 ng/mL; isolated increase in AF CXCL10 concentration: CXCL10 ≥2.2 ng/mL; increase in both AF IL‐6 and CXCL10 concentrations: IL‐6 ≥2.6 ng/mL and CXCL10 ≥2.2 ng/mL. Acute chorioamnionitis: the presence of acute chorioamnionitis ≥stage 2 in the absence of chronic chorioamnionitis; chronic chorioamnionitis: the presence of chronic chorioamnionitis in the absence of acute chorioamnionitis ≥stage 2; placental lesions associated with maternal anti‐fetal rejection: chronic chorioamnionitis, villitis of unknown etiology (VUE), and chronic deciduitis with plasma cells. None of the patients grouped by their normal AF IL‐6 and CXCL10 concentrations had both acute and chronic placental inflammatory lesions; therefore, the computation of the odds ratios relative to the common reference cannot be performed. Red values indicate statistically significant associations between the study group on the left and the outcome named in the column header