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Horm Metab Res 2001; 33(6): 348-353
DOI: 10.1055/s-2001-15420
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Luteal Phase of the Menstrual Cycle in Young Healthy Women is Associated with Decline in Interleukin 2 Levels

P. Trzonkowski1 , J. Myśliwska2 , K. Łukaszuk3 , E. Szmit1 , E. Bryl2 , A. Myśliwski1
  • 1 Department of Histology, Medical University of Gdańsk, Gdańsk, Poland
  • 2 Department of Immunology, Medical University of Gdańsk, Gdańsk, Poland
  • 3 Department of Endocrinology, Institute of Obstetrics Gynaecology, Medical University of Gdańsk, Gdańsk, Poland
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Publication History

Publication Date:
31 December 2001 (online)

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The aim of this study was to look at the possible changes in the blood levels of Interleukin 2 (IL2) during the sexual cycle in generally healthy, young, regularly menstruating women. The concentrations of progesterone and 17β-estradiol were measured using radioimmunological assay. The bioactivity of interleukin 2 was measured using a biological test on the IL2-sensitive CTLL cell line. The percentage of lymphocytes with intracellular IL2 was determined by flow cytometry. Eighteen healthy volunteers (19 - 29 years old) were examined on days 5, 8, 14, 18 and 25 of the same cycle. All women were characterised by a regular menstrual cycle as per physiological levels of 17β-estradiol and progesterone. The luteal phase of the cycle was characterised by both a decrease of IL2 blood levels and a decrease in the percentage of intracellular IL2-containing lymphocytes stimulated in vitro. The IL2 level fluctuations observed during the menstrual cycle may be one factor causing pre-menstrual infections observed in young women. On the other hand, the decrease of IL2 may be seen as a start of the immune suppression necessary for an embryo’s nidation.

Key words:

Interleukin 2 - Menstrual Cycle - Intracellular Cytokines - Flow Cytometry

References

  • 1 Haus E, Smolensky M H. Biologic rhythms in the immune system.  Chronobiol Int. 1999;  16 (5) 581-622
    PubMedSearch in Google Scholar
  • 2 Brannstrom M, Friden B E, Jasper M, Norman R J. Variations in peripheral blood levels of immunoreactive tumour necrosis factor alpha (TNF alpha) throughout the menstrual cycle and secretion of TNF alpha from the human corpus luteum.  Eur J Obstet Gynecol Reprod Biol. 1999;  83 (2) 213-217
    CrossrefPubMedSearch in Google Scholar
  • 3 Myśliwska J, Trzonkowski P, Bryl E, Łukaszuk K, Myśliwski A. Lower interleukin 2 and higher tumor necrosis factor α levels are associated with perimenstrual recurrent facial herpes simplex infection in young women.  Eur Cytokine Network. 2000;  11 (3) 397-406
    PubMedSearch in Google Scholar
  • 4 Maskill J K, Laird S M, Okon M, Li T C, Blakemore A I. Stability of serum interleukin-10 levels during the menstrual cycle.  Am J Reprod Immunol. 1997;  38 (5) 339-342
    PubMedSearch in Google Scholar
  • 5 Angstwurm M W, Gartner R, Ziegler-Heitbrock H W. Cyclic plasma IL-6 levels during normal menstrual cycle.  Cytokine. 1997;  9 (5) 370-374
    CrossrefPubMedSearch in Google Scholar
  • 6 Chiu K M, Arnaud C D, Ju J, Mayes D, Bacchetti P, Weitz S, Keller E T. Correlation of estradiol, parathyroid hormone, interleukin-6, and soluble interleukin-6 receptor during the normal menstrual cycle.  Bone. 2000;  26 (1) 79-85
    CrossrefPubMedSearch in Google Scholar
  • 7 Makinoda S, Mikuni M, Sogame M, Kobamatsu Y, Furuta I, Yamada H, Yamamoto R, Fujimoto S. Erythropoietin, granulocyte-colony stimulating factor, interleukin-1 beta and interleukin-6 during the normal menstrual cycle.  Int J Gynaecol Obstet. 1996;  55 (3) 265-271
    CrossrefPubMedSearch in Google Scholar
  • 8 Jilma B, Dirnberger E, Loscher I, Rumplmayr A, Hildebrandt J, Eichler H G, Kapiotis S, Wagner O F. Menstrual cycle-associated changes in blood levels of interleukin-6, alpha1 acid glycoprotein, and C-reactive protein.  J Lab Clin Med. 1997;  130 (1) 69-75
    CrossrefPubMedSearch in Google Scholar
  • 9 Agarwal S K, Marshall G D, Jr. Perimenstrual alterations in type-1/type-2 cytokine balance of normal women.  Ann Allergy Immunol Asthma. 1999;  83 (3) 222-228
    PubMedSearch in Google Scholar
  • 10 Di Rosa R, Amoroso A, Ferri G M, Di Rosa E, Tanzilli O, Afeltra A, Reverberi L, Startari S. Changes in various immunological parameters in patients with recurrent vaginal candidiasis.  Boll Ist Sieroter Milan. 1991 - 92;  70 (1 - 2) 499-504
    PubMedSearch in Google Scholar
  • 11 Mulero-Marchese R D, Blank K J, Sieck T G. Strain-dependent migration of lymphocytes to the vaginal mucosa after peripheral immunization.  Immunogenetics. 1999;  49 (11 - 12) 973-980
    CrossrefPubMedSearch in Google Scholar
  • 12 Corrigan E M, Clancy R L, Dunkley M L, Eyers F M, Beagley K W. Cellular immunity in recurrent vulvovaginal candidiasis.  Clin Exp Immunol. 1998;  111 574-578
    CrossrefPubMedSearch in Google Scholar
  • 13 Kalo-Klein A, Witkin S S. Candida albicans - cellular immune system interactions during different stages of the menstrual cycle.  Am J Obstet Gynecol. 1989;  161 1132-1136
    PubMedSearch in Google Scholar
  • 14 Wise S L, Yarbrough J A, Stafford C T, Leffell M S, Thompson W O, Ades E W. In vitro effects of interleukin-2 and gamma globulin on immune dysfunction in a patient with severe mucocutaneous herpes simplex virus infection.  Ann Allergy. 1992;  68 47-52
    PubMedSearch in Google Scholar
  • 15 Rinaldo C R, Torpey D J. Cell-mediated immunity and immunosuppression in herpes simplex virus infection.  Immunodeficiency. 1993;  5 33-90
    PubMedSearch in Google Scholar
  • 16 Heeg K, Reimann J, Kabelitz D, Hardt C, Wagner H. A rapid colorimetric assay for the determination of IL-2-producing helper T cell frequencies.  J Immunol Methods. 1985;  77 237-246
    CrossrefPubMedSearch in Google Scholar
  • 17 Struth H S. Flow cytometry: Rapid biochemical analysis of single cells.  Anal Biochem. 1982;  125 225-242
    CrossrefPubMedSearch in Google Scholar
  • 18 Maccio A, Mantovani G, Turnu E, Artini P, Contu G, Volpe A. Preovulatory human follicular fluid in vitro inhibits Interleukin IL-1alpha, IL-2, and production and expression of p55 chain IL-2 receptor of lymphomonocytes.  Fertil Steril. 1994;  62 327-332
    PubMedSearch in Google Scholar
  • 19 Brannstrom M, Wang L, Norman R J. Ovulatory effect of interleukin-1 beta on the perfused rat ovary.  Endocrinology. 1993;  132 (1) 399-404
    CrossrefPubMedSearch in Google Scholar
  • 20 Stone B A, Koopersmith T B, Quinn K, Quinn P, Marrs R P. Levels of interleukin-2 receptor in serum of patients during the menstrual cycle and following embryo/gamete transfer.  Am J Reprod Immunol. 1989;  20 (3) 114-116
    PubMedSearch in Google Scholar
  • 21 Montgomery Rice V, Limback S D, Roby K F, Terranova P F. Differential responses of granulosa cells from small and large follicles to follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity: effects of tumour necrosis factor-alpha.  Hum Reprod. 1998;  13 (5) 1285-1291
    CrossrefPubMedSearch in Google Scholar
  • 22 Wang L J, Norman R J. Concentrations of immunoreactive interleukin-1 and Interleukin-2 in human preovulatory follicular fluid.  Hum Reprod. 1998;  7 147-150
    PubMedSearch in Google Scholar
  • 23 Piccinni M P, Giudizi M G, Giannarini L, Sampognaro S, Parronchi P, Manetti R, Annunziato F, Livi C et al. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones.  J Immunol 1995;. 1;  155 (1) 128-133
    PubMedSearch in Google Scholar
  • 24 Le N, Yousefi S, Vaziri N, Carandang G, Ocariz J, Cesario T. The effect of beta-estradiol, progesterone and testosterone on the production of human leukocyte derived interferons.  J Biol Regul Homeost Agents. 1988;  2 (4) 199-204
    PubMedSearch in Google Scholar
  • 25 Kwiatkowski B, Artrip J H, Michler R E, Itescu S. Human NK cells demonstrate increased adherence and lysis of porcine endothelium following activation with IL-2.  Ann Transplant. 1997;  2 21-25
    PubMedSearch in Google Scholar
  • 26 Feinberg B B, Tan N S, Gonik B,Brath P C, Walsh S W. Increased progesterone concentrations are necessary to suppress interleukin-2-activated human mononuclear cell cytotoxicity.  Am J Obstet Gynecol. 1991;  165 1872-1876
    PubMedSearch in Google Scholar
  • 27 Genazzani A R, Lemarchand-Beraud T, Aubert M L, Felber J P. Pattern of plasma ACTH, hGH, and cortisol during menstrual cycle.  J Clin Endocrinol Metab. 1975;  41 (3) 431-437
    PubMedSearch in Google Scholar
  • 28 Honda M. The simultaneous assay of progesterone, 17-hydroxyprogesterone, and deoxycorticosterone in human plasma by competitive protein binding.  Endocrinol Jpn. 1976;  23 (3) 259-264
    PubMedSearch in Google Scholar
  • 29 Myśliwska J, Zorena K, Bąkowska A, Skuratowicz-Kubica A, Myśliwski A. Significance of tumor necrosis factor alpha in patients with long-standing type-I diabetes mellitus.  Horm Metab Res. 1998;  30 (3) 158-161
    PubMedSearch in Google Scholar
  • 30 Norbiato G, Bevilacqua M, Vago T, Taddei A, Clerici L. Glucocorticoids and the immune function in the human immunodeficiency virus infection: a study in hypercortisolemic and cortisol-resistant patients.  J Clin Endocrinol Metab. 1997;  82 (10) 3260-3263
    CrossrefPubMedSearch in Google Scholar
  • 31 Arzt E, Paez Pereda M, Costas M, Sauer J, Renner U, Holsboer F, Stalla G K. Cytokine expression and molecular mechanisms of their auto/paracrine regulation of anterior pituitary function and growth.  Ann N Y Acad Sci. 1998;  840 525-531
    PubMedSearch in Google Scholar
  • 32 Raghupathy R. Th1-type immunity is incompatible with successful pregnancy.  Immun Today. 1997;  18 (10) 478-482
    PubMedSearch in Google Scholar
  • 33 Lim K J, Odukoya O A, Ajjan R A, Li T C, Weetman A P, Cooke I D. The role of T-helper cytokines in human reproduction.  Fertil Steril. 2000;  73 (1) 136-142
    CrossrefPubMedSearch in Google Scholar
  • 34 Lopez C, Kirkpatrick D, Read S E, Fitzgerald P A, Pitt J, Pahwa S, Ching C Y, Smithwick E M. Correlation between low natural killing of fibroblasts infected with herpes simplex virus type 1 and susceptibility to herpes virus infections.  J Infect Dis. 1983;  147 1030-1035
    PubMedSearch in Google Scholar
  • 35 Leszczyszyn-Pynka M. [Natural cytotoxicity of peripheral blood mononuclear cells in Herpes simplex and Varicella-zoster virus infections].  Acta Haematol Pol. 1995;  26 393-402
    PubMedSearch in Google Scholar
  • 36 Kuo Y C, Lin C Y, Cheng S F, Lin C C, Liu W T. Impaired natural killer cytotoxicity during recrudescence of recurrent herpes simplex virus type 1 infection.  Cancer Detect Prev. 1987;  Suppl 1 51-55
    PubMedSearch in Google Scholar
  • 37 Bigda J, Myśliwski A. Indomethacin inhibits kidney metastasis in bomirski melanoma-bearing hamsters, and modulates natural killer cytotoxic activity of tumor hosts in vivo and in vitro.  Anticancer Res. 1998;  18 3549-3554
    PubMedSearch in Google Scholar
  • 38 Kuo Y C, Lin C Y. Recurrent herpes simplex virus type 1 infection precipitated by the impaired production of interleukin-2, alpha-interferon, and cell-mediated cytotoxicity.  J Med Virol. 1990;  31 183-189
    PubMedSearch in Google Scholar

P. Trzonkowski,M.D. 

Department of Histology
Medical University of Gdańsk

ul. De¿binki 1
80-210 Gdańsk
Poland


Email: E-mail:ptrzon@amedec.amg.gda.pl