CLINICAL IMMUNOLOGY
Cytokines in the blood and semen of infertile patients
 
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Submission date: 2014-11-21
 
 
Final revision date: 2015-05-08
 
 
Acceptance date: 2015-05-11
 
 
Publication date: 2015-10-15
 
 
Cent Eur J Immunol 2015;40(3):337-344
 
KEYWORDS
ABSTRACT
Cytokines have been important mediators of the immunity and can be involved in numerous processes in the male genital tract including acting as immunomodulatory elements within the male gonad.
The aims of this study were: 1) to detect pro- and anti-inflammatory cytokine levels in the control group and subgroups of infertile men; and 2) to set up the practical recommendations concerning determination of cytokine levels for the male infertility diagnosis.
Observations were performed in a group of 82 men: healthy controls (n = 27) and infertile patients (n = 55). The male infertility group was further subdivided into patients with: varicocele (n = 22), idiopathic infertility (n = 13) and partners of couples with recurrent spontaneous abortion (RSA; n = 20). Semen analysis was determined following WHO criteria. The cytokine interleukin 1β (IL-1β), IL-6, IL-10, IL-18; tumor necrosis factor  (TNF-), interferon γ (IFN-γ) and transforming growth factor β1 (TGF-β1) contents in serum and seminal plasma were determined by quantitative ELISA.
An interesting marker of male infertility appears to be TGF-β1 (blood) significantly elevated in idiopathically infertile males and in the RSA group. Besides elevated TGF-β1 in a group of idiopathic infertility significantly elevated IL-10, IL-18, IFN-γ (blood) and statistically decreased IL-1β while increased IFN-γ were revealed in seminal plasma compared to healthy controls.
We may postulate novel cytokine micropatterns for patients with different background of infertility. Therefore, circulating cytokines: IL-1β IL-10, IL-18, TGF-β1, IFN-γ and IL-1β, IFN-γ and TGF-β1 in seminal plasma should be extended in evaluation of specific types of male infertility.
REFERENCES (49)
1.
Iammarone E, Balet R, Lower AM, et al. (2003): Male infertility. Best Pract Res Clin Obstet Gynaecol 17: 211-229.
 
2.
Ji G, Long Y, Zhou Y, et al. (2012): Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility. BMC Med 10: 49.
 
3.
Jungwirth A, Giwercman A, Tournaye H, et al. (2012): European Association of Urology guidelines on Male Infertility: the 2012 update. Eur Urol 62: 324-332.
 
4.
Moraes AJ, Bonfa E, Cocuzza M, et al. (2010): Gonad evaluation in male dermatomyositis. A pilot study. Clin Exp Rheumatol 28: 441-442.
 
5.
Moraes AJ, Pereira RM, Cocuzza M, et al. (2008): Minor sperm abnormalities in young male postpubertal patients with juvenile dermatomyositis. Braz J Med Biol Res 41: 1142-1147.
 
6.
Silva CA, Bonfa E, Ostensen M (2010): Maintance of fertility in patients with rheumatic diseases needing anti-inflammatory and immunosupressive drugs. Arthritis Care Res (Hoboken) 62: 1682-1690.
 
7.
Silva CA, Hallak J, Pasqualotto FF, et al. (2002): Gonadal function in male adolescents and young males with juvenile onset systemic lupus erytematosus. J Rheumatol 29: 2000-2005.
 
8.
Suchiro RM, Borba EF, Bonfa E, et al. (2008): Testicular Sertoli cell function in male systemic lupus erythematosus. Reumatology (Oxford) 47: 1692-1697.
 
9.
Silva CA, Cocuzza M, Borba EF, Bonfa E (2012): Cutting-Edge Issues in Autoimmune Orchitis. Clinic Rev Allerg Immunol 42: 256-263.
 
10.
Al-Daghistani HI, Hamad AWR, Abdel-Dayem M, et al. (2010): Evaluation of serum testosterone, progesterone, seminal antisperm antibody, and fructose levels among Jordanian males with a history of infertility. Biochem Res Int 2010: 409640.
 
11.
Kursh ED (1987): What is the incidence of varicocele in a fertile population? Fertil Steril 48: 511.
 
12.
Ficarra V, Porcaro AB, Righetti R, et al. (2002): Antegrade scrotal sclerotherapy in the treatment of varicocele: a prospective study. BJU Int 89: 264-268.
 
13.
Pasqualotto FF, Sundaram A, Sharma RK, et al. (2008): Semen quality and oxidative stress scores in fertile and infertile patients with varicocoele. Fertil Steril 89: 602-607.
 
14.
Domes T, Kirk SLo, Grober ED, et al. (2012): The incidence and effect of bacteriospermia and elevated seminal leukocytes on semen parameters. Fertil Steril 97: 1050-1055.
 
15.
Kokab A, Akhondi MM, Sadeghi MR, et al. (2010): Raised inflammatory markers in semen from men with asymptomatic chlamydial infection. J Androl 31: 114-120.
 
16.
Martinez-Prado E, Camejo Bermúdez MI (2010): Expression of IL-6, IL-8, TNF-αlpha, IL-10, HSP-60, anti-HSP-60 antibodies, and anti-sperm antibodies, in semen of men with leukocytes and/or bacteria. Am J Reprod Immunol 63: 233-243.
 
17.
Pacey AA (2012): Assessment of male factor. Best Pract Res Clin Obstet Gynaecol 26: 739-746.
 
18.
Fraczek M, Czernikiewicz A, Kurpisz M (2012): Cytokines and Oxidative Stress in the Germ Line. Chapter 9 in A. Agarwal et al. (eds). Studies on Men’s Health and fertility, Oxidative Stress in Applied Basic research and Clinical Practice. DOI 10.1007/978-1-61779-776-7-9, Springer Science + Business Media, LLC 2012; 179-205.
 
19.
Hedger M, Klug J, Fröhlich S, et al. (2005): Regulatory cytokine expression and interstitial fluid formation in the normal and inflamed rat testis are under Leydig cell control. J Androl 26: 379-386.
 
20.
O’Bryan MK, Hedger MP (2008): Inflammatory networks in the control of spermatogenesis: chronic inflammation in an immunologically privileged tissue? Adv Exp Med Biol 636: 92-114.
 
21.
Maegawa M, Kamada M, Irahara M, et al. (2002): A repertoire of cytokines in human seminal plasma. J Reprod Immunol 54: 33-42.
 
22.
Politch JA, Tucker L, Bowman FP, Anderson DJ (2007): Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 22: 2928-2035.
 
23.
Qian L, Sun G, Zhou B, et al. (2011): Study on the Relationship Between Different Cytokines in the Semen of Infertility Patients. Am J of Reprod Immunol 66: 157-161.
 
24.
Jacobo P, Guazzone VA, Theas MS, Lustig L (2011): Testicular autoimmunity. Autoimmun Rev 10: 201-204.
 
25.
Xia W, Mruk DD, Lee WM, Cheng CY (2005): Cytokines and junction restructuring duringspermatogenesis – a lesson to learn from the testis. Cytokine Growth Factor Rev 16: 469-493.
 
26.
Cavalcanti MC, Steilmann C, Falling K, et al. (2011): Apoptotic gene expression in potentially fertile and subfertile men. Mol Hum Reprod 17: 415-420.
 
27.
Cheng CY, Mruk DD (2010): A local autocrine axis in the testes that regulates spermatogenesis. Nat Rev Endocrinol 6: 380-395.
 
28.
Li MW, Mruk DD, Lee WM, Cheng CY (2009): Cytokines and the junction restructuring events during spermatogenesis in the estis: an emerging new concept of regulation. Cytokine Growth Factor Rev 20: 329-238.
 
29.
Gonzalez CR, Matzkin ME, Frungieri MB, et al. (2010): Expression of the TGF-beta1 system in human testicular pathologies. Reprod Biol Endocrinol 8: 148.
 
30.
Camejo MI, Segnini A, Proverbio F (2001): Interleukin-6 (IL-6) in seminal plasma of infertile men, and lipid peroxidation of their sperm. Arch Androl 47: 97-101.
 
31.
Eggert-Kruse W, Kiefer I, Beck C, et al. (2007): Role for tumor necrosis factor alpha (TNF-αlpha) and interleukin 1-beta (IL-1beta) determination in seminal plasma during infertility investigation. Fertil Steril 87: 810-823.
 
32.
Jiwakanon J, Berg M, Persson E, et al. (2010): Cytokine expression in the gilt oviduct: effects of seminal plasma, spermatozoa and extender after insemination. Anim Reprod Sci 119: 244-257.
 
33.
O’Leary S, Armstrong DT, Robertson SA (2011): Transforming growth factor-β (TGF-β) in porcine seminal plasma. Reprod Fertil Dev 23: 748-758.
 
34.
Vera O, Vasqucz LA, Munos MG (2003): Semen quality and presence of cytokines in seminal fluid of bull ejaculates. Theriogenology 60: 553-558.
 
35.
Eggert-Kruse W, Boit R, Rohr G, et al. (2001): Relationship of seminal plasma interleukin (IL)-8 and IL-6 with semen quality. Hum Reprod 16: 517-528.
 
36.
Furuya Y, Akashi T, Fuse H (2003) Soluble Fas and interleukin-6 and interleukin-8 levels in seminal plasma of infertile men. Arch Androl 49: 449-452.
 
37.
Matalliotakis IM, Cakmak H, Fragouli Y, et al. (2006): Increased IL-18 levels in seminal plasma of infertile man with genital tract infections. Am J Reprod Immunol 55: 428-433.
 
38.
Sanocka D, Jedrzejczak P, Szumała-Kaekol A, et al. (2003): Male genital tract inflammation: the role of selected interleukins in regulation of pro-oxidant and antioxidant enzymatic substances in seminal plasma. J Androl 24: 448-455.
 
39.
Lotti F, Corona G, Mancini M, et al. (2011): Ultrasonographic and clinical correlates of seminal plasma interleukin-8 levels in patients attending an andrology clinic for infertility. Int.
 
40.
J Androl 34: 600-613.
 
41.
Li H, Shang X, Huang Y (2004): The effects of interleukin-10 and -8 in chronic prostatitis. Zhonghua Nan Ke Xue 10: 486-487, 490.
 
42.
Zhang J, Gao J (2004): Determination of IL-1 beta, IL-4 and IL-10 contents in the seminal plasma of infertile patients and its clinical value. Zhonghua Nan Ke Xue 10: 851-854.
 
43.
Carp HJA, Selmi C, Shoenfeld Y (2012): The autoimmune bases of infertility and pregnancy loss. J Autoimmun 38: j266-j274.
 
44.
Terayama H, Naito M, Qu N, et al. (2011): Intratesticular expression of mRNAs of both interferon γ and tumor necrosis factor  is significantly increased in experimental autoimmune orchitis in mice. J Reprod Dev 57: 296-302.
 
45.
Bezold G, Politch JA, Kiviat NB, et al. (2007): Prevalence of sexually transmissible pathogens in semen from asymptomatic male infertility patients with and without leukocytospermia. Fertil Steril 87: 1087-1097.
 
46.
Kopa Z, Wenzel J, Papp GK, Haidl G (2005): Role of granulocyte elastase and interleukin-6 in the diagnosis of male genital tract inflammation. Andrologia 37: 188-194.
 
47.
Lazaros LA, Xita NV, Chatzikyriakidou AL, et al. (2012): Association of TNF, TNFR1 and TNFR2 polymorphisms with sperm concentration and motility. J Andrology 33: 74-80.
 
48.
Naz RK, Evans L (1998): Presence and modulation of interleukin-12 in seminal plasma of fertile and infertile men. J Androl 19: 302-307.
 
49.
Komsky A, Huleihel M, Ganaiem M, et al. (2012): Presence of IL-18 in testicular tissue of fertile and infertile men. Andrologia 44: 1-8.
 
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