{"paper_id":"05dd8069-7149-447f-886c-d8b96c6108fa","body_text":"http://www.revistadechimie.ro REV .CHIM.(Bucharest)♦70♦ No. 8 ♦20192944\n*email: atudor@umft.ro; Phone:(+40)724206748;        tliviu33@yahoo.com; Phone: (+40)0744764737\nPro-inflammatory Cytokines (IL6, IL8 and TNF-ααααα) in the\nEvaluation of Ovarian Endometriosis Cyst\nCAROLINA GOBJILA 1#, MARIUS LUCIAN CRAINA 1#, DANIELA OANA TOADER 2#, IZABELLA PETRE 1,\nCORNELIU BOGDAN ANDOR 3#,  ANCA TUDOR 4*, ROXANA RAMONA ONOFREI 5#, LIVIU ATHOS TAMAS 6*,\nADRIAN COSMIN ILIE 7\n1University of Medicine and Pharmacy Victor Babes Timisoara, Department XII, Discipline of Obstetrics and Gynecology,\n2 Eftimie Murgu Sq., 300041,Timisoara, Romania\n2 National Institute for Mother and Child Health, Alessandrescu – Rusescu Bucharest, Polizu Clinical Hospital,  38-52 Gheorghe\nPolizu Str., 022455, Bucharest, Romania\n3University of Medicine and Pharmacy Victor Babes Timisoara, Department XV of Orthopedics, Traumatology, Urology and\nMedical Imaging, Timisoara, Romania\n4University of Medicine and Pharmacy Victor Babes Timisoara, Department of Functional Sciences, Medical Informatics and\nBiostatistics Discipline, 2 Eftimie Murgu Sq., 300041,Timisoara, Romania\n5University of Medicine and Pharmacy Victor Babes Timisoara, Department of Rehabilitation, Physical Medicine and Rheumatology,\n2 Eftimie Murgu Sq., 300041,Timisoara, Romania\n6University of Medicine and Pharmacy Victor Babes Timisoara, Department II, Discipline of Biochemistry and Pharmacology,\n2 Eftimie Murgu Sq., 300041, Timisoara, Romania\n7University of Medicine and Pharmacy Victor Babes Timisoara, Department of Anatomy and Embryology, 2 Eftimie Murgu Sq.,\n300041, Timisoara, Romania\nEndometriosis is the abnormal growth of cells (endometrial cells) similar to those that form the inside of\nthe uterus, but in a location outside of the uterus. Endometriosis is most commonly found on other organs\nof the pelvis. These lesions are most commonly found on the ovaries, the Fallopian tubes, the surface of the\nuterus, the bowel, and on the membrane lining of the pelvic cavity (i.e. the peritoneum). We corroborate\nTNF-α, IL-6 and IL-8 markers with intraoperative laparoscopic on 39 patients diagnosed with endometriosis\nin January 2016 - December 2017, aged 20-45 years. There has been a preoperative evaluation in the\npatients from this that included the anamnesis, clinical examination and laboratory tests. Anamnesis recorded\ndemographic details, patient’s personal, physiological and pathological medical history. Evaluation of\npreoperative investigations consisted of general and local systems examination, a gynecological examination\nin order to identify the specific signs of endometriosis. Making matters worse is that endometriosis exhibits\nsignificant immunological dysfunction, including the over-expression of pro-inflammatory cytokines like\ninterleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF), all of which contribute to a chronic\nup-regulation of painful, tissue-damaging inflammatory processes. Because the cause of endometriosis is\npoorly understood, there are no known ways to prevent its development.\nKey words: ovarian endometriosis cyst, pro-inflammatory cytokines, IL6, IL8, TNF- α\nEndometriosis is defined as the presence of endometrial\ntissue outside of the uterus. Unfortunately, this pathology\nis more common in fertile people aged 16-50 years,\ncharacterized by increasingly worsened pain and\nsubfertility [1-2]. Women with endometriosis have\nsymptoms that include chronic pelvic pain, dysmenorrhea\nand dyspareunia, that significantly reduce the quality of\ntheir life.\nIn the pathogenesis of endometriosis inflammation\nplays an important role. Infiltration of local pro-\ninflammatory mediators in the peritoneal environment\naffects ovarian function and anatomy of the pelvis. All these\noutlines, later, the picture of symptomatic endometriosis.\nPathophysiological, there is an acute inflammation followed\nby macrophage infiltration, tissue remodelling and\nneovascularization [3].\nThe responses to the inflammatory process are directly\ncorrelated with the growth of activated macrophages and\ncytokines secreted into the peritoneal fluid, thereby\nproducing maintenance of endometrioses by endometrial\nadhesion, invasion, angiogenesis and endometrial cell\nproliferation within endometrial deposits [4-6].\nAlthough the pathogenesis of endometriosis is still\ncontroversial, a widely accepted explanation is that of\nSampson’s theory according to which the flow of\nmenstrual blood determines the displacement and storage\nof endometrial cells at unusual locations (Sampson’s\ntheory of retrograde menstruation).\nThere are numerous studies that report that a series of\nbiomarkers (IL-6, IL-8, TNF- α, high sensitivity C-reactive\nprotein and antigens CA125 and CA19-9) show with high\nsensitivity and correlated with clinical symptoms the\nclinical forms of endometriosis.\nExperimental part\nMaterial and methods\nIn our study group of 39 patients diagnosed with ovarian\nendometriosis cyst, the dosage of immunological markers\nand cytokine IL-6, IL-8 and TNF- α levels in serum was\nperformed preoperatively and 6 months after surgery. We\ncompared marker values for patients diagnosed with\nendometriosis with those of a control group (26 cases) to\nwhom this diagnosis was not confirmed. The data was\nprocessed using SPSS v17 statistical package software.\n\nREV .CHIM.(Bucharest)♦70♦No. 8 ♦2019 http://www.revistadechimie.ro 2945\nThe numerical variables were compared with the\nnonparametric Mann-Whitney U test (in the case of two\nindependent groups). For p<0.05 were considered\nstatistical significance [7-8].\nResults and discussion s\nEndometriosis is a polygenic disease with a complex,\nmultifactorial ethology that affects approximately 10% of\nreproductive-age women. Women with endometriosis\nhave symptoms that include chronic pelvic pain,\ndysmenorrhea and dyspareunia, that significantly reduce\nthe quality of their life [9-10]. Endometriosis is also the\nmain cause of infertility in women, the prevalence rate\nranging from 20 to 50% [11-12].\nIn order to describe the IL - 6, IL - 8 and TNF values we\ncalculated the central tendency and dispersion parameters\nand we plotted the recommended figures (tables 1-3,\nfigures 1- 4).\nTable 1\nVALUES OF CENTRAL AND DISPERSION TREND INDICATORS FOR THE IL-6\nVARIABLE\nFig. 1. The normal Q-Q plots for the IL - 6 values\nIL-6 values for the patients in the study\ngroup do not follow a normal distribution\n(Shapiro-Wilk normality test, p = 0.038).\nIL-6 values for patients in the control group\ndo not follow a normal distribution\n(Shapiro-Wilk normality test, p <0.001).Table 2\nVALUES OF CENTRAL AND DISPERSION TREND INDICATORS FOR THE\nTNF VARIABLE\nTNF values for patients in the control\ngroup follow a normal distribution\n(Shapiro-Wilk normality test, p = 0.239).\nTNF values for the patients in the study\ngroup follow a normal distribution\n(Shapiro-Wilk normality test, p = 0.815).\nFig. 2.  The normal Q-Q plots for\nthe TNF values\n\nhttp://www.revistadechimie.ro REV .CHIM.(Bucharest)♦70♦ No. 8 ♦20192946\nTable 3\nVALUES OF CENTRAL AND DISPERSION TREND\nINDICATORS FOR THE IL-8 VARIABLE\nFig. 3.The normal Q-Q plots\nfor the IL - 8 values\nIL-8 values for patients in the control group do\nnot follow a normal distribution (Shapiro-Wilk\nnormality test, p < 0.001)\nIL-8 values for the patients in the study\ngroup do not follow a normal distribution\n(Shapiro-Wilk normality test, p < 0.001)\nFig. 4. The histogram and the\nBox plot for the I - 6, TNF and\nIL - 8\nThe histograms of IL-6 values compared to the\ntwo samples\nBox Plot representation of IL-6 values\ncompared to the two samples\nThe Histograms of TNF values compared to the two\nsamples\nBox Plot representation of TNF values\ncompared to the two samples\nFig.5\n\nREV .CHIM.(Bucharest)♦70♦No. 8 ♦2019 http://www.revistadechimie.ro 2947\nIL-6 values are significantly increased for the study group\ncompared to control (Mann-Whitney U Test, p = 0.001).\nTNF values for the endometriosis group are\ninsignificantly low (Unpaired t Test, p=0.072) (fig.5).\nIL-8 values are significantly increased for the study group\ncompared to control (Mann-Whitney U Test, p < 0.001)\n(fig. 6).\nConclusions\nPro-inflammatory cytokines appear to play an important\nrole in the development of endometriosis, initially acting\nlocally and then manifesting systemically, thus rendering\nthe clinical picture of endometriosis. The high prevalence\nand severe consequences of this disease caused ta major\npublic health issue in modern society. And yet, the\nmechanism responsible for the initiation and development\nof this disease still remains an enigma.\nIdentifying a non-invasive diagnostic marker for\nendometriosis could facilitate the early diagnosis of this\npathology and early medical management with an\nappropriate treatment for each case.\nReferences\n1.YAGMUR E, BASTU E, KARAMUSTAFAOGLU-BALCI B, et al. Non-\ninvasive diagnosis of endometriosis based on  a combined analysis of\nfour plasma biomarkers. Centr Eur J Immunol. 38:154–158, 2013.\n2.MOINI A, MALEKZADEH F , AMIRCHAGHMAGHI E, et al. Risk factors\nassociated with endometriosis among infertile Iranian women. Arch\nMed Sci., 9:506–514, 2013.\n3.CUFF J, LONGA CRE T.A. Endometriosis does not confer improved\nprognosis in ovarian carcinoma of uniform cell type. Am J Surg\nPathol.May;36(5), 2012.\n4.GOBJILA, C., ANASTASIU D., CRAINA M., CITU I., CITU C., PANTEA\nS., PETRE I., Correlations between Clinical and Imaging in Diagnosis\nof Endometriosis - Case Report, The 13th Conference of the\nRomanian-German Society of Obstetrics and Gynecology,Timiºoara,\nRomania, 14-16 September 2017, pag 151- 153, Ed. Filodiritto Editore\nProceeding, 2017.\nFig.6\nThe Histograms of IL-8 values compared to the\ntwo samples\nBox Plot representation of IL-8 values\ncompared to the two samples\n5.PETRE I., CRAINA M., BERNAD E., MOLERIU L.C., CITU I., CITU C.,\nSTELEA L., GOBJILA C., BOGLUT A., CRACIUN L., PANTEA S.,\nImmunological Markers and Inflammatory Cytokines in Endometriosis,\nThe 13th Conference of the Romanian-German Society of Obstetrics\nand Gynecology,Timiºoara, Romania, 14-16 September 2017, pg 243-\n248, Ed. Filodiritto Editore Proceeding, 2017.\n6.GOBJILA C., PETRE I., CRAINA M., IONITA I., MOLERIU R.D., BOGLUT\nA., MILOICOV O.C. BACEAN, CRACIUN L., Corroboration of Ultrasound\nAspects with the AL CA -125 Seric Levels and with Intraoperative\nLaparoscopic Images in Cases of Pelvic Endometriosis, 5th Congress\nOf The Romanian Society Of Ultrasound In Obstetrics and Gynecology,\nFilodiritto Editore Proceeding, Targu Mures, Romania, pg 487- 491,\n2017.\n7.GOBJILA C., CRAINA M., PETRE I., IACOB R., POP E., BOLINTINEANU\nS.L., MOLERIU L.C., TIMAR B., TIMAR R., PANTEA S. - Clinical Features,\nMr Imaging Findings and Pathologic Correlation in the Diagnosis of\nEndometriosis, The 4 th Congress of the Romanian  Society for Minimal\nInvasive Surgery in  Gynecology, Annual Days of the National Institute\nfor Mother and Child Health Alessandrescu–Rusescu,  1-3 November,\n2018,  Bucharest, Romania, pag 277-283, Ed. Filodiritto Editore\nProceedings, 2019.\n8.GOBJILA C., CRAINA M., PETRE I., IACOB R., POP E., BOLINTINEANU\nS.L., STOIAN D., MOLERIU R.D., TIMAR B., TIMAR R., PANTEA S. - The\nStudy of Biomarkers for the Ovarian Endometriotic Cyst Pathology,\nThe 4 th Congress of the Romanian  Society for Minimal Invasive\nSurgery in  Gynecology, Annual Days of the National Institute for\nMother and Child Health Alessandrescu–Rusescu,  1-3 November,\n2018,  Bucharest, Romania, pag  292-297, Ed. Filodiritto Editore\nProceedings, ISBN 978-88-85813-48-9, 2019.\n9.LIN SC, LI YH, WU MH, et al. Suppression of COUP-TFII by pro-\ninflammatory cytokines contributes to the pathogenesis of\nendometriosis. J Clin Endocrinol Metab. 2014;99:e427e437\n10.NOMURA H, OKUDA K, SAITO N, et al. Mini-laparoscopic surgery\nversus conventional laparoscopic surgery for patients with\nendometriosis. Gynecol Minim Invasive Ther. 2013;2:85e88.\n11.MIHALYI A, GEVAERT O, KYAMA CM, et al. Non-invasive diagnosis\nof endometriosis based on a combined analysis of six plasma\nbiomarkers. Hum Reprod ;25:654e664, 2010.\n12.SEEBER B, SAMMEL MD, FAN X, et al. Panel of markers can\naccurately predict endometriosis in a subset of patients. Fertil Steril.\n89:1073e1081, 2008.\nManuscript received:17.01.2019","source_license":"CC0","license_restricted":false}