Serum Cytokines As Biomarkers for Nonsurgical Prediction of Endometriosis

Objective: To test the ability of a group of serum cytokines, either individually or in combination, to serve as biomarkers for the nonsurgical diagnosis of endometriosis.

Study Design: Subjects were allocated to two groups according to their laparoscopic diagnosis. The first group consisted of patients with endometriosis and the second group was made up of infertile women with no pelvic pathology (controls). Blood samples were collected preoperatively and stored. Cytokines were measured in the serum of all participants using the Bio-Plex Protein Array System. Nonparametric statistics and the Mann-Whitney test were used to compare groups. Subjects were seen at the Gynecologic endoscopy unit.

Results: Three cytokines were significantly higher in the serum of subjects with endometriosis than in the control group: interleukin-6 (IL-6) [4.41 pg/ml (range: 1.47-15.01) versus 0.97 pg/ml (range: 0.29-2.98), respectively; p<0.001], monocyte chemotactic protein-1 (MCP-1) [37.91 pg/ml (range: 24.54-94.74) versus 22.13 pg/ml (range: 13.85-39.45), respectively; p<0.001], and interferon-gamma (INF-gamma) [19.01 pg/ml (range: 1.19-73.52) versus 0.30 pg/ml (range: 0.00-13.05), respectively; p<0.001]. There was no statistically significant difference between subjects with endometriosis and controls in the serum concentration of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), or granulocyte macrophage colony stimulating factor (GM-CSF). Interleukin-2 (IL-2), interleukin-8 (IL-8), and interleukin-15 (IL-15) were undetectable in the serum of both groups. None of the measured cytokines showed significant correlation with the cycle phase or stage of endometriosis. In a multivariate analysis, serum interleukin-6 provided a sensitivity of 71% and a specificity of 66% to discriminate between endometriosis patients and controls at a cutoff point of 1.9 pg/ml. Adding monocyte chemotactic protein-1 and interferon-gamma to interleukin-6 did not increase the discriminative ability over that achieved by measuring serum interleukin-6 alone.

Conclusions: Serum of subjects with endometriosis contains significantly higher levels of interleukin-6, monocyte chemotactic protein-1, and interferon-gamma than control women. Serum interleukin-6 measurements discriminate between women with endometriosis and controls. Interleukin-6 provides a promising serum marker for the nonsurgical prediction of endometriosis.