CYTOKINE EXPRESSION PROFILES OF PERITONEAL FLUID IN THE PATIENTS WITH UTERINE LEIOMYOMA
https://doi.org/10.15789/1563-0625-2006-4-547-556
Abstract
Abstract. Uterine leiomyoma (UL) is a hormone-dependent benign tumor of uterus. Social significance of UL is stipulated by its high rate among fertile females. Scarce data exist about the impact of cytokines in UL progression. Th1/Th2 paradigm is one of crucial points in modern immunology. Evaluation of cytokines involved into either type of immune response is of special significance for studying the diseases accompanied by the changes of extracellular matrix, e.g., leiomyomas. In present study, we analyzed peritoneal fluids from UL patients, with multiplex detection of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, GM-CSF, IFN-γ and TNF-α (Th1/Th2 panel), by means of a Bio-Plex® instrument (Bio-Rad, USA). Twenty-seven patients were observed in our study (20 patients with UL, and 7 myoma-free women (a group of comparison). The mean age of the patients was 43.5±0.6 years. The duration of UL ranged from 0 to 18 years. As a result, the levels of IL-10, GM-CSF, IFN-γ and TNF-α in patients with long-existing UL (over 5 years) were significantly higher (p<0,05) than in group with a disease story of <5 years. IFN-γ values in peritoneal fluid patients with UL did inversely correlate with uterine size. Moreover, the levels of IFN-γ in patients with smaller uterine volume (<8 weeks of pregnancy) were increased in relation to the group with larger tumor size. IL-10 contents were increased in the patients with adenomyosis, rapid and slow growth of UL, and in both types of tumor (simple and proliferative). Increased IL-5 levels were observed in the patients with single tumor nodules (as related to the patients bearing multiple nodes, and comparison group). Furthermore, intramural and subserosal location of nodes was characterized by increased levels of IL-5. In the patients free of adenomyosis, IL-5 value was increased against the comparison group. The changes in IL-2, IL-4, IL-12 and IL-13 levels in patients with UL were not statistically significant.
About the Authors
K. A. SyssoevRussian Federation
N. V. Kulagina
Russian Federation
Areg A. Totolian
Russian Federation
References
1. Аревадзе И.Э. Особенности функционального состояния и апоптоза иммунокомпетентных клеток периферической крови и перитонеальной жидкости у женщин с лейомиомой матки: Автореф. дис....канд. мед. наук. - Иваново, 2003. - 23 с.
2. Леваков С.А. Диагностика простой и пролиферирующей миомы матки //Вестник новых медицинских технологий. - 2000. - Т.VII, №2. - С. 82-86.
3. Малышкина А.И., Аревадзе И.Э., Анциферова Ю.С., Суворкина Е.Е. Особенности функционального состояния иммунокомпетентных клеток периферической крови у женщин с малыми миомами матки /Материалы II-го Российского форума «Мать и дитя». - М., 2000. - С. 244.
4. Суворкина Е.Е. Значение иммунологических факторов в патогенезе быстрорастущей лейомиомы матки: : Автореф. дис....канд. мед. наук. - Иваново, 2003. - 23 с.
5. Ярилин А.А. Основы иммунологии. - М.: Медицина, 1999. - 608с.
6. Зуева Е.Е., Кулагина Н.В., Комарова Л.С., Куртова А.В., Молчанова И.В., Алексеева Е.Ф., Тотолян Арег А. Представленность различных популяций лимфоцитов в периферической крови больных миомой матки // Мед. иммунология. - 2005. - № 5-6. - С. 532-542.
7. Морозова Е.Б., Чухловин А.Б., Тотолян Арег. А. Прогностическая значимость генного полиморфизма ММП-1, ММП-3 и MTHFR в развитии лейомиомы матки // Журнал акушерства и женских болезней - 2005. - Т.54. - Вып.3. - С.54-59.
8. Hrycek A., Cuzytek A., Tustanowski J. Immunological disorders in patients with uterine myomas //Wiad-Lek. - 2000. - V.53. - №5-6. - P.271-276.
9. Sikorski R., Kapec E., Zaleska W. Serum levels of proinflammatory cytokines in women with uterine myomas //Ginecol Pol. - 2001; 72 (12A). - P.1485-1488.
10. Shaw R.W. Gonadotropin hormone-releasing hormone analogue treatment of fibroids //Baillier’s Clinical. Obstetrics, Gynaecology. - 1998. - Vol.12. - №2. - P.245-267.
11. Ding L., Xu J., Luo X., Chegini N. Gonadotropin releasing hormone and transforming growth factor beta activate mitogen-activated protein kinase/ extracellularly regulated kinase and differentially regulate fibronectin, type I collagen, and plasminogen activator inhibitor-1 expression in leiomyoma and myometrial smooth muscle cells // J. Clin Endocrinol Metab. - 2004. - Vol.89. - N11. - P.5549-5557.
12. Punnonen R., Teisala K., Kuoppala T., Bennett B, Punnonen J. Cytokine production profiles in the peritoneal fluids of patients with malignant or benign gynecologic tumors // Cancer - 1998. - Vol.83. - N4. - P.788-796.
13. Lee B.S., Nowak R.A. Human leiomyoma smooth muscle cells show increased expression of transforming growth factor-beta 3 (TGF beta 3) and altered responses to the antiproliferative effects of TGF beta // J Clin Endocrinol Metab. - 2001. - Vol.86. - N2. - P.913-920.
14. Gomez-Torres M.J., Acien P., Campos A., Velasco I. Embryotoxicity of peritoneal fluid in women with endometriosis. Its relation with cytokines and lymphocyte populations // Hum Reprod. - 2002. Vol.17. - N3. - P.777-781.
15. Goh K.C., Haque S.J., Williams B.R. p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons. // EMBO J. - 1999. - Vol.18. - N20. - P.5601-5608.
16. Shim J.H., Xiao C., Paschal A.E., Bailey S.T., Rao P., Hayden M.S., Lee K.Y., Bussey C., Steckel M., Tanaka N., Yamada G., Akira S., Matsumoto K., Ghosh S. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo // Genes Dev. - 2005. - Vol.19. - N22. - P.2668-2681. Epub 2005 Oct 31.
17. Buttice G., Miller J., Wang L., Smith B.D. Interferon-gamma induces major histocompatibility class II transactivator (CIITA) that mediates collagen repression and major histocompatibility class II activation by human aortic smooth muscle cells // Circ Res. - 2006. - Jan 26. [Epub ahead of print]
18. Ghosh A.K., Bhattacharyya S., Mori Y., Varga J. Inhibition of collagen gene expression by interferon-gamma: Novel role of the CCAAT/enhancer bind- ing protein beta (C/EBPbeta) // J Cell Physiol. - 2006. - Vol.207. - N1. - P.251-260.
19. Xu Y., Wang L., Buttice G., Sengupta P.K., Smith B.D. Interferon gamma repression of collagen (COL1A2) transcription is mediated by the RFX5 complex // J Biol Chem. - 2003. - Vol.278. - N49. - P.49134-49144.
20. Gu L., Zhu Y.J., Guo Z.J., Xu X.X., Xu W.B. Effect of IFN-gamma and dexamethasone on TGF-beta1-induced human fetal lung fibroblast-myofibroblast differentiation// Acta Pharmacol Sin. - 2004. - Vol.25. - N11. - P.1479-1488.
21. Antsiferova Y.S., Sotnikova N.Y., Posiseeva L.V., Shor A.L. Changes in the T-helper cytokine profile and in lymphocyte activation at the systemic and local levels in women with endometriosis // Fertil Steril. - 2005. - Vol.84. - N6. - P.1705-1711.
22. Lee K.S., Baek D.W., Kim K.H., Shin B.S., Lee D.H., Kim J.W., Hong Y.S., Bae Y.S., Kwak J.Y. IL-10-dependent down-regulation of MHC class II expression level on monocytes by peritoneal fluid from endometriosis patients // Int Immunopharmacol. - 2005. - Vol.5. - N12. - P.1699-1712.
23. Tabibzadeh S., Becker J.L., Parsons A.K. Endometriosis is associated with alterations in the relative abundance of proteins and IL-10 in the peritoneal fluid // Front Biosci. - 2003. - Vol.1. - N8. - P.a70-78.
24. Vang R., Medeiros L.J., Samoszuk M., Deavers M.T. Uterine leiomyomas with Eosinophils: a clinicopathologic study of 3 cases // Int J Gynecol Pathol. - 2001. - Vol.20. - N3. - P.239-243.
25. Buka N.J. Eosinophilia associated with uterine leiomyomas //Can Med Assoc J. - 1965. - Vol.93. - N24. - P.163-165.
Review
For citations:
Syssoev K.A., Kulagina N.V., Totolian A.A. CYTOKINE EXPRESSION PROFILES OF PERITONEAL FLUID IN THE PATIENTS WITH UTERINE LEIOMYOMA. Medical Immunology (Russia). 2006;8(4):547-556. (In Russ.) https://doi.org/10.15789/1563-0625-2006-4-547-556