The expression and significance of leukemia inhibitory factor, interleukin-6 and vascular endothelial growth factor in Chinese patients with endometriosis

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Leukemia inhibitory factor, interleukin-6, and vascular endothelial growth factor levels are elevated in endometriosis patients, with LIF and IL-6 synergistically increasing VEGF in stromal cells, potentially contributing to disease development.

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This study measured leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, matched eutopic endometrium, and ectopic versus eutopic endometrial stromal cells from 31 Chinese patients with endometriosis undergoing laparoscopic surgery, compared with 32 controls undergoing laparoscopic surgery for uterine fibroids or ovarian tumors. Patients with endometriosis had higher LIF, IL-6, and VEGF levels in both blood and peritoneal fluid than controls, with peritoneal fluid levels higher than blood, and ectopic lesions showed higher LIF and IL-6 mRNA but lower VEGF mRNA than matched eutopic tissue. In vitro, treating cultured ectopic endometrial stromal cells with LIF, IL-6, or both increased VEGF protein in the supernatant, supporting a synergistic effect on VEGF secretion. The paper’s limitation is that it assesses associations and short-term cell stimulation rather than establishing causal mechanisms in vivo. This paper is centrally about endometriosis — it characterizes LIF, IL-6, and VEGF expression in endometriotic compartments and tests how they regulate VEGF in endometrial stromal cells.

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Abstract

Objective To observe the levels of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, and ectopic endometrial stromal cells of patients with endometriosis, and to compare expression of IL-6, LIF and VEGF expression between endometriotic and non-endometriotic patients underwent laparoscopic surgery.

Methods

Thirty-one patients who underwent laparoscopic surgery for endometriosis in our hospital from January 2018 to January 2020 were included in the observation group, and 32 patients who underwent laparoscopic surgery for uterine fibroids, ovarian serous cystadenoma, and ovarian teratomas, were included in the control group. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the two groups of patients were detected. The levels of LIF, IL-6 and VEGF in ectopic endometrial tissue and self-paired eutopic endometrial tissue, ectopic endometrial stromal cells and self-paired eutopic endometrial stromal cells of patients in the observation group were detected. After treating the primary cultured ectopic endometrial stromal cells with LIF and IL-6 alone or in combination, the changes of VEGF mRNA of ectopic endometrial stromal cells and the VEGF levels in the supernatant were observed.

Results

The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the observation group were all higher than those of the control group (P < 0.05), and the levels of LIF, IL-6 and VEGF in the peritoneal fluid of the observation group were significantly higher than those in the blood (P < 0.05). In the observation group, the expression levels of LIF-mRNA and IL-6 mRNA in the ectopic endometrial tissue were higher than those in the self-paired eutopic endometrial tissues (P < 0.05), while the expression level of VEGF mRNA in the ectopic endometrial tissues was lower than that in the self-paired eutopic endometrial tissues (P < 0.05). Besides, the mRNA expression levels of LIF, IL-6 and VEGF in ectopic endometrial stromal cells of the observation group were all higher than those in the self-paired eutopic endometrial stromal cells (P < 0.05). After stimulating ectopic endometrial stromal cells with LIF, IL-6 and LIF + IL-6, respectively, the VEGF levels in the supernatant were all significantly higher than that in the blank control group (P < 0.05).

Conclusion

The LIF, IL-6 and VEGF levels in blood and peritoneal fluid were increased in patients with endometriosis, and increased LIF and IL-6 in ectopic endometriosis stromal cells can play a synergistic role in increasing the VEGF levels, which may be involved in the occurrence and development of endometriosis. Similar content being viewed by others Data availability The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

References

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Nat Immunol 16(5):448–457 Funding No funding was received for this study. Author information Authors and Affiliations Contributions CL and HY contributed to the conception and design of the study; HLZ, YJL, YYZ and HYL performed the experiments. CL and FZF collected and analyzed data; CL and HY wrote the manuscript; all authors reviewed and approved the final version of the manuscript. Corresponding author Ethics declarations Conflict of interest The authors declare that they have no competing interests. Ethics approval and consent to participate The study protocol was approved by the Ethics Committee of Linyi Central Hospital (No.LY19-208). Written informed consent was obtained from all the study subjects before enrollment. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Li, C., Zhao, HL., Li, YJ. et al. The expression and significance of leukemia inhibitory factor, interleukin-6 and vascular endothelial growth factor in Chinese patients with endometriosis. Arch Gynecol Obstet 304, 163–170 (2021). https://doi.org/10.1007/s00404-021-05980-5 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00404-021-05980-5

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Asian People Endometriosis Endometrium Interleukin-6 Leukemia Inhibitory Factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Adult Asian People China China Endometriosis Endometriosis Endometriosis Endometrium Female Humans Interleukin-6 Laparoscopy Laparoscopy

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