Inflammatory cytokine profile of VEGF and IL-6 from the endometrium of women with and without endometriosis

Ashish Ashish; Kusum Kusum; Sangeeta Rai; Kulsoom Zahra; Surendra Pratap Mishra; Gunjan Rai; Radha Chaube; Royana Singh

doi:10.18203/2320-1770.ijrcog20210717

Authors

Ashish Ashish MRU Lab, Department of Anatomy, Banaras Hindu University, Varanasi, Uttar Pradesh, India http://orcid.org/0000-0002-6844-1289
Kusum Kusum Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Sangeeta Rai Department of Obstetrics and Gynecology, Banaras Hindu University, Varanasi, Uttar Pradesh, India http://orcid.org/0000-0003-3952-228X
Kulsoom Zahra Department of Biochemistry, Institute of Medical Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Surendra Pratap Mishra Department of Biochemistry, Institute of Medical Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Gunjan Rai MRU Lab, Department of Anatomy, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Radha Chaube Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Royana Singh MRU Lab, Department of Anatomy, Banaras Hindu University, Varanasi, Uttar Pradesh, India http://orcid.org/0000-0002-2115-774X

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20210717

Keywords:

Cytokine, Endometriosis, Infertility, Inflammation, IL-6, VEGF

Abstract

Background: Endometriosis affects an estimated 176 million women worldwide, which constitutes 10% of the total female population causing debilitating symptoms of pelvic pain and infertility, which limits the quality of reproductive life of affected women. The present study aimed to assess the serum level of VEGF and pro-inflammatory marker IL-6 in cases and normal healthy control groups.

Methods: VEGF and IL-6 serum levels were measured by competitive sandwich enzyme-linked immunosorbent assay (ELISA) from 34 subjects with surgically confirmed endometriosis, 16 subjects with adenomyosis and 18 similar age matched healthy controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. Patients were characterized in terms of their socio-demographic and clinically diagnosed characteristics, including the validated infertility and chronic disease registries.

Results: The mean serum level of VEGF was significantly (p<0.0001) higher in case of endometriosis (3887 ng/l) followed by adenomyosis (2588 ng/l) group and lower in case of normal healthy control (665 ng/l) group. The mean serum IL-6 was found to be highly significant (p<0.0001) in case of endometriosis (90.49 pg/ml) followed by adenomyosis (70.37 pg/ml) group and lower in case of normal healthy control (22.97 pg/ml) group.

Conclusions: VEGF and IL-6 seems to play a crucial role in the implantation and development of endometriotic lesions, and the disease is associated with significant modulations in the serum levels of VEGF. IL-6 can be a reliable non-invasive diagnostic marker for endometriosis.

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Author Biography

Ashish Ashish, MRU Lab, Department of Anatomy, Banaras Hindu University, Varanasi, Uttar Pradesh, India

MRU Lab, Department of Anatomy, Institute of Medical Science, Banaras Hindu University.

References

Klemmt PA, Starzinski-Powitz A. Molecular and cellular pathogenesis of endometriosis. Curr Womens Health Rev. 2017;13(999):1-11.

Kusum, Rai S, Chaube R. Endometriosis: role of aromatase and recent advances in the disease treatment. Austin J Obs Gynecol. 2019;6(2).

Riazi H, Tehranian N, Ziaei S, Mohammadi E, Hajizadeh E, Montazeri A. Clinical diagnosis of pelvic endometriosis: A scoping review. BMC Womens Health. 2015;15(1):01.

Saceanu SM, Patrascu S, Patrascu A, Surlin V. Endometriosis: when and how we treat. Fertil Orient Female Reprod Surg. 2017:61.

Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789-99.

Adaji E, Ahankari A, Myles P. An investigation to identify potential risk factors associated with common chronic diseases among the older population in India. Indian J Community Med. 2017;42(1):46-52.

Hsu AL, Khachikyan I, Stratton P. Invasive and noninvasive methods for the diagnosis of endometriosis. Clin Obstet Gynecol. 2010;53(2):413-9.

Ashish A, Kusum K, Rai S, Singh R. Endometriosis a brief review: evaluation of crucial risk factors and current treatment regimes. Int J Adv Med. 2020;7(12):1896.

Carpinello OJ, Sundheimer LW, Alford CE, Taylor RN, De Cherney AH, Feingold KR, et al. Endometriosis- Endotext; 2000.

Acién P, Velasco I. Endometriosis: a disease that remains enigmatic. ISRN Obstet Gynecol. 2013;2013:1-12.

Audebert A. Endometriosis. In: Encyclopedia of Endocrine Diseases. MDText.com, Inc.; 2018: 498-505.

Miller JE, Monsanto SP, Ahn SH, Khalaj K, Fazleabas AT, Young SL, et al. Interleukin-33 modulates inflammation in endometriosis. Scient Rep. 2017;7(1):1-1.

Kyama CM, Debrock S, Mwenda JM, D’Hooghe TM. Potential involvement of the immune system in the development of endometriosis. Reprod Biol Endocrinol. 2003;1.

Bulun SE. Endometriosis. In: Yen and Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. 8th edn. Elsevier Inc.; 2019:609-42.e7.

de Almeida Asencio F, Ribeiro HA, Ayrosa Ribeiro P. Symptomatic endometriosis developing several years after menopause in the absence of increased circulating estrogen concentrations: a systematic review and seven case reports. Gynecol Surg. 2019;16(1):1-11.

Shigesi N, Kvaskoff M, Kirtley S. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(4):486-503.

Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Prim. 2018;4(1):9.

Vallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis. Hum Reprod Update. 2019;25(5):565-92.

Malutan AM, Drugan T, Costin N, Ciortea R, Bucuri C, Rada MP, Mihu D. Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis. Cent Eur J Immunol. 2015;40(1):96.

Malutan A, Drugan T, Georgescu C, Ciortea R, Bucuri C, Bobric A, et al. Vascular Endothelial Growth Factor serum levels in women with advanced endometriosis. Acta Endocrinol. 2016;12(1):7.

Gagné D, Pagé M, Robitaille G, Hugo P, Gosselin D. Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis. Hum Reprod. 2003;18(8):1674-80.

Ferrara N. Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int. 1999;56(3):794-814.

Lin YH, Chen YH, Chang HY, Au HK, Tzeng CR, Huang YH. Chronic niche inflammation in endometriosis-associated infertility: Current understanding and future therapeutic strategies. Int J Mol Sci. 2018;19(8).

Wu MH, Hsiao KY, Tsai SJ. Endometriosis and possible inflammation markers. Gynecol Minim Invasive Ther. 2015;4(3):61-7.

Wu MH, Wang CA, Lin CC, Chen LC, Chang WC, Tsai SJ. Distinct regulation of cyclooxygenase-2 by interleukin-1β in normal and endometriotic stromal cells. J Clin Endocrinol Metab. 2005;90(1):286-95.

Li S, Fu X, Wu T, Yang L, Hu C, Wu R. Role of interleukin-6 and its receptor in endometriosis. Med Sci Monit. 2017;23:3801-7.

As-Sanie S, Black R, Giudice LC, Valbrun TG, Gupta J, Jones B, et al. Assessing research gaps and unmet needs in endometriosis. Am J Obstet Gynecol. 2019;221(2):86-94.

Donnez J. Introduction: From pathogenesis to therapy, deep endometriosis remains a source of controversy. Fertil Steril. 2017;108(6):869-71.

Foti PV, Farina R, Palmucci S, Vizzini IA, Libertini N, Coronella M, et al. Endometriosis: clinical features, MR imaging findings and pathologic correlation. Insights Imag. 2018;9(2):149-72.

Eisenberg VH, Weil C, Chodick G, Shalev V. Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members. BJOG Int J Obstet Gynaecol. 2018;125(1):55-62.

Moradi M, Parker M, Sneddon A, Lopez V, Ellwood D. Impact of endometriosis on women’s lives: a qualitative study. BMC Womens Health. 2014;14(1):123.

Ashish A, Kusum K, Rai S, Singh R. Endometriosis a brief review: evaluation of crucial risk factors and current treatment regimes. Int J Adv Med. 2020;7(12):1896.

Tsudo T, Harada T, Iwabe T, Tanikawa M, Nagano Y, Ito M, et al. Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues. Fertil Steril. 2000;73(2):205-11.

Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, et al. The pathogenesis of endometriosis: Molecular and cell biology insights. Int J Mol Sci. 2019;20(22).

Martinez S, Garrido N, Coperias JL, Pardo F, Desco J, Garcia-Velasco JA, et al. Serum interleukin-6 levels are elevated in women with minimal-mild endometriosis. Hum Reprod. 2007;22(3):836-42.

Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011;2(12):1097-105.

McLaren J, Prentice A, Charnock-Jones DS, Millican SA, Müller KH, Sharkey AM, et al. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest. 1996;98(2):482-9.

McLaren J. Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update. 2000;6(1):45-55.