A low-grade chronic inflammation in polycystic ovary syndrome: Role of interleukin-1 alpha, 1 beta, 17A and TNFα

Document Type : Original Article

Authors

1 Assistant Professor, Vali-e-Asr Reproductive Health Research Center, Vali-e-Asr Hospital, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

2 Assistant Professor, Department of Pathology, School of Medicine, Pathology laboratory of Vali-e-Asr Hospital, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

3 Instructor, Department of Community Medicine, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.

4 MSc. of Midwifery, Vali-e-Asr Reproductive Health Research Center, Vali-e-Asr Hospital, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Introduction: Polycystic ovary is a range of endocrinal and metabolic disorders in the complicated patients. Studies in recent decades report that chronic low-grade inflammation is due to this syndrome being long-term. This study was performed with the aim to evaluate the role of the immune system and the regulatory role of cytokines of Tumor necrosis factor-alpha, Interlukins of 1alpha, 1beta, and 17 A in the patients with polycystic ovary in order to more knowing about these relationships be effective in the etiology or cause of polycystic ovary syndrome and consequently, effective drug-therapy be possible.
Methods: This study was performed on the patients referred to …. Infertility center in 2012. 85 patients with infertility caused by polycystic ovarian syndrome were placed in intervention group and 86 cases in control group. Four cytokines of 1alpha, 1beta, 17 A and tumor necrosis factor alpha were evaluated in blood serum of both groups. Data was analyzed using SPSS software (version 19), and t test, chi-square and Mann-Whitney tests. PResults: Interlukin 1 (alpha, beta) was higher PCO group than control group, this difference was completely clear in interleukin 1α (P<0.001) and increased interleukin 1beta was also significant (P=0.017). Inflammatory mediator of IL-17 was significantly lower in serum of patients with PCOS than control group (P<0.001). TNFα mediator showed no significant change in two groups (P=0.119).
Conclusion: Polycystic ovaries can be a mild chronic inflammatory disease. Because cytokines 1 alpha and beta, particularly alpha, show greatly increased in these patients.

Keywords

References

  1. Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2011; 162(2): CD007506.
  2. Fleming R, Hopkinson ZE, Wallace AM, Greere IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clinical Endocrinol Metab 2002; 87(2): 569-74.
  3. Walsh LJ, Trinchieri G, Waldorf HA, Whitaker D, Murphy GF (May 1991). Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1. Proc Natl. Acad Sci USA 1991; 88(10):4220–4.
  4. Ihnatko R, Kubes M. TNF signaling: early events and phosphorylation. Gen Physiol. Biophys. 2007; 26(3):159–67.
  5. Samy N1, Hashim M, Sayed M, Said M. Clinical significance of inflammatory markers in polycystic ovary syndrome: their relationship to insulin resistance and body mass index. Dis Markers 2009; 26(4):163-70.
  6. Brocker C, Thompson D, Matsumoto A, Nebert DW, Vasiliou V. Evolutionary divergence and functions of the human interleukin (IL) gene family. Human Genomics 2010; 5 (1): 30–55.
  7. Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, et al. cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science,1988; 241 (4865): 585–9.
  8. Liu C, Hart RP, Liu XJ, Clevenger W, Maki RA, De Souza EB. Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA. J. Biol Chem 1996; 271 (34): 20965–72.
  9. Ben Menachem-Zidon O, Avital A, Ben-Menahem Y, Goshen I, Kreisel T, Shmueli EM, Segal M, et al. Astrocytes support hippocampal-dependent memory and long-term potentiation via interleukin-1 signaling. Brain Behav Immun 2011; 25 (5): 1008–16.
  10. Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G, et al. Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus 2003; 13 (7): 826–34.
  11. Gurney AL, Aggarwal S.  IL-17: prototype member of an emerging cytokine family. J Leukoc Biol 2002; 71(1):1–8.
  12. Wang X, Zhang Y, Yang XO,  Nurieva RI, Chang SH, Ojeda SS, et al. Transcription of Il17 and Il17f are controlled by conserved noncoding sequence 2. Immunity 2012; 36(1): 23–31.
  13. Ishigame H, Kakuta S, Nagai T,  Kadoki M, Nambu A, Komiyama Y, et al. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 2009; 30(1):108–119.
  14. Jin W, Dong C. IL-17 cytokines in immunity and inflammation. Emerging Microbes & Infections 2013; 2: e60.
  15. Sukhikh GT, Vanko LV. Interrelationships between immune and reproductive systems in human. Russ J Immunol 1999; 4: 312–4.
  16. Tada T. The immune system as a supersystem. Annu Rev Immunol 1997; 15:1–13.
  17. Besedovsky HO, del Rey AE, Sorkin E, Da Prada M, Burri R, Honegger C. The immune response evokes changes in brain noradrenergic neurons. Science 1983; 221(4610): 564–6.
  18. Marks BR1, Craft J. Barrier immunity and IL-17. Semin Immunol 2009; 21(3):164-71.
  19. The Rotterdom ESHRE/Asrm-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome (PCOS) 2004. Human Reprod 19(1):41-7. 
  20. Cohen I, Rider P, Carmi Y, Braiman A, Dotan S, White MR, et al. Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc Natl Acad Sci USA 2010; 107(6): 2574-9.
  21. Bloomgarden Z.T. Inflammation and insulin resistance. Diabetes Care 2003: 26(6): 1922 –6.
  22. Frishman WF. Biologic markers as predictors of cardiovascular disease. Am J Med. 1998; 104 (6): 18S–27S.
  23. Orio F.Jr, Palomba S, Cascella T. The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90(1): 2–5.
  24. Elenkov I.J, Wilder R.L. Chrousos G.P, Vizi E.S. The Sympathetic Nerve—An Integrative Interface between Two Supersystems: The Brain and the Immune System .Pharmacological Review. 2000; 52(4): 595-638.
  25. Sverrisdottir YB, Mogrent T, Kataoka J, Janson PO, Stener-Victorin E. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth?. Am J Physiol Endocrinol Metab 2008; 294(3): E576–81.
  26. Effect of Ramadan Fasting on Activity of Hypothalamus-Pituitary-Adrenal Axis in Polycystic Ovary Syndrome Patients. The Iranian Journal of Obstetrics, Gynecology and fertility 2012; 16(57):7-16.
  27. Smagin GN, Swiergiel AH, Dunn AJ. Peripheral administration of interleukin-1 increases extracellular concentrations of norepinephrine in rat hypothalamus: comparison with plasma corticosterone. Psychoneuroendocrinology 1996; 21(1): 83-93.
  28. Chuluyan H, Saphier D, Rohn W, Dunn AJ. Noradrenergic innervation of the hypothalamus participates in the adrenocortical responses to interleukin-1. Neuroendocrinology 1992; 56(1): 106–11.
  29. Kolbus A1, Walch K, Nagele F, Wenzl R, Unfried G, Huber JC. Interleukin-1 alpha but not interleukin-1 beta gene polymorphism is associated with polycystic ovary syndrome. J Reprod Immunol 2007; 73(2): 188-93.
  30. Atsumi T, Singh R, Sabharwal L, Bando H, Meng J, Arima Y, et al. Inflammation amplifier, a new paradigm in cancer biology. Cancer Res 2014; 74(1): 8-14.
  31. Besedovsky H.O, Sorkin E, Keller M, Mtiller J. Hormonal changes during the immune response. Proc Soc Exp Biol 1975; 150: 466-70.
  32. Shek P.N, Sabiston B.H. Neuroendocrine regulation of immune processes: change in circulating corticosterone levels induced by the primary antibody response in mice. Int J Immunopharmacol 1983; 5(1):23-33.
  33.  Normann S, Besedovsky H, Schardt M, del Rey A. Interactions between endogenous glucocorticoids and inflammatory responses in normal and tumor-bearing mice: role of T cells. J Leukocyte Biol 1998; 44(6):551-8.
  34. Besedovsky HO, Del Rey A, Sorkin E, Dinarello CA. Immunoregulatory feedback between Interleukin-1 and glucocorticoid hormones. Science 1987; 233(4764): 652-54
  35. Angeli A1, Masera RG, Sartori ML, Fortunati N, Racca S, Dovio A, et al. Modulation by cytokines of glucocorticoid action. Ann N Y Acad Sci 1999; 876: 210-20.
  36. Pasquali R, Gambineri A. Cortisol and the Polycystic Ovary Syndrome. Expert Rev oEndocrinol  Metab 2012; 7(5): 555-66.
  37. Milutinović DV, Macut D, Božić I, Nestorov J, Damjanović S, Matić G. Hypothalamic-pituitary-adrenocortical axis hypersensitivity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2011; 119(10): 636-43.
  38. Lansdown A, Rees DA. The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?. Clin Endocrinol (Oxf) 2012; 77(6): 791-801.
  39. Bosmann M, Meta F, Ruemmler R, Haggadone MD, Sarma JV, Zetoune FS, et al. Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice. Am J Pathol 2013;182(4):1124-30.
  40. Nakanishi m, Furuno T. Molecular Basis of Neuroimmune Interaction in an In Vitro Coculture Approach. Cell Mol Immunol 2008; 5(4):249-59.

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