Subscribe to RSS
DOI: 10.1055/s-0030-1262763
© Georg Thieme Verlag KG Stuttgart ˙ New York
Verschiebung des Verhältnisses von Inflammationsmarkern in einem Kollektiv mit polyzystischem Ovariensyndrom (PCOS)
Shift in the Relation of Inflammatory Markers in a Collective with Polycystic Ovary Syndrome (PCOS)Publication History
Publication Date:
11 February 2011 (online)
Zusammenfassung
Patientinnen mit polyzystischem Ovariensyndrom (PCOS) weisen neben Reproduktionsstörungen Symptome des metabolischen Syndroms wie erhöhtes kardiovaskuläres Risiko und Adipositas auf. Eine akute Zunahme der Fettzellmasse infolge einer Adipositas geht mit einer vermehrten Inflammation durch den Anstieg von proinflammatorischen Zytokinen einher. Zytokine des Typs 1 und Typs 2 sowie Proinflammationsmarker wurden in einem Kollektiv von 58 PCOS-Patienten und 133 Alters- und BMI-angepassten Kontrollen mittels Multiplex-Immunoassay bestimmt. Typ-1-Zytokine IL2 und IL12 wiesen im Gegensatz zu INFγ; im Serum der PCOS-Patienten und Kontrollen keine signifikante Veränderung auf. Allerdings waren die Typ-2-Zytokine IL4, IL5 oder IL10 und die Proinflammationsmarker IL6, TNFα oder IL1β bei den PCOS-Patienten signifikant erhöht. Zieht man die Relation der Typ-1-Zytokine IL2 und IL12 zu Typ-2-Zytokinen IL1β, IL5, IL10 in Betracht, konnte bei den PCOS-Patientinnen eine drastische Reduktion dieses Quotienten beobachtet werden. Dies wurde, wenn auch mit einem geringeren Faktor für IL4 und IL6 ermittelt. Die für PCOS spezifischen Relationen zu INFγ fokussieren sich auf IL7, IL8 und IL1β aber auch auf IL5. Die vorliegende Untersuchung des PCOS-Kollektivs zeigt, dass das Sezernierungsmuster und besonders das Verhältnis von Zytokinen ein Spezifikum für PCOS ist und somit möglicherweise hieraus eine prädiktive Funktion abgeleitet werden kann.
Abstract
Patients with polycystic ovary syndrome (PCOS) suffer next to reproductive disturbances from symptoms of the metabolic syndrome like elevated coronary risk and obesity. An increase in fat cell mass as consequence of obesity is associated with an increase of inflammation by elevation of proinflammatory cytokines. Type 1 and type 2 cytokines as well as proinflammatory markers were investigated in a collective of 58 PCOS patients and 133 age and BMI matched controls by a multiplex immuno-assay. Type 1 cytokines IL2 and IL12 in contrast to INFγ did not significantly alter in serum of PCOS patients compared to controls. Type 2 cytokines like IL4, IL5 or IL10 and the proinflammatory markers IL6, TNFα or IL1β were elevated in PCOS patients. Considering the relation of type 1 cytokine IL2 and IL12 to type 2 cytokines especially IL5, IL10 and IL1β, indicated that the quotient was drastically reduced in PCOS patients. This holds also true for IL4 and IL6 but to a lower degree. The relation to INFγ reveals a different, nevertheless PCOS specific picture, focusing on IL7, IL8, IL1γ and IL5. The study presented indicates that the pattern and especially the relation of cytokine sezernation are specific and might be useful as a predictive to PCOS.
Schlüsselwörter
PCOS - Inflammation - Typ-1- / Typ-2-Zytokine - Th1- / Th2-System - Adipositas
Key words
PCOS - inflammation - type 1 / type 2 cytokine - th1 / th2 balance - obesity
Literatur
- 1 Salesi M, Bravo-Vera R, Sheikh A et al. Pathogenesis of the polycystic ovary syndrome: What is the role of obesity?. Metabolism. 2004; 53 358-376
- 2 Venkatesan A M, Dunaif A, Corbould A. Insulin resistance in polycystic ovary syndrome: progress and paradoxes. Recent Prog Horm Res. 2001; 56 295-308
- 3 Azziz R. PCOS: A diagnostic challenge. Reprod Biomed Online. 2004; 8 644-648
- 4 O'Meara N M, Blackman J D, Ehrmann D A et al. Defects in beta-cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1993; 76 1241-1247
- 5 Hudecova M, Holte J, Olovsson M et al. Long-term follow-up of patients with polycystic ovary syndrome: reproductive outcome and ovarian reserve. Hum Reprod. 2009; 24 1176-1183
- 6 Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX?. Trends Endocrinol Metab. 2003; 14 365-370
- 7 Rebuffé-Scrive M, Cullberg G, Lundberg P A et al. Anthropometric variables and metabolism in polycystic ovarian disease. Horm Metab Res. 1989; 21 391-397
- 8 Rajkhowa M, Neary R H, Kumpatla P et al. Altered Composition of High Density Lipoproteins in Women with the Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism. 1997; 82 3389-3394
- 9 Cinti S, Mitchell G, Barbatelli G et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005; 46 2347-2355
- 10 Kidd P. Th1 / Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003; 8 223-246
- 11 Singh V K, Mehrotra S, Agarwal S S. The paradigm of Th1 and Th2 cytokines: its relevance to autoimmunity and allergy. Immunol Res. 1999; 20 147-161
- 12 Jäger A, Kuchroo V K. Effector and Regulatory T-cell Subsets in Autoimmunity and Tissue Inflammation. Scand J Immunol. 2010; 72 173-184
- 13 Moser M, Murphy K M. Dendritic cell regulation of TH1-TH2 development. Nat Immunol. 2000; 1 199-205
- 14 Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003; 3 133-146
- 15 Gonzalez F, Thusu K, Abdel-Rahman E et al. Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome. Metabolism. 1999; 48 437-441
- 16 Kelly C C, Lyall H, Petrie J R et al. Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 2001; 86 2453-2455
- 17 Escobar-Morreale H F, Villuendas G, Botella-Carretero J I et al. Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women. Diabetologia. 2003; 46 625-633
- 18 Mohlig M, Spranger J, Osterhoff M et al. The polycystic ovary syndrome per se is not associated with increased chronic inflammation. Eur J Endocrinol. 2004; 150 525-532
- 19 Puder J J, Varga S, Kraenzlin M et al. Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance. J Clin Endocrinol Metab. 2005; 90 6014-6021
- 20 Hahn S, Fingerhut A, Khomtsiv U et al. The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with polycystic ovary syndrome. Clin Endocrinol (Oxf).. 2005; 62 573-579
- 21 Song Y, Simonyi K, Thomas R et al. Simultaneous quantitation of 5 phosphorylated proteins using the Bio-Plex Protein Array System. Bio-Rad Bull. 2000; 2632
- 22 Kellar K L, Iannone M A. Multiplexed microsphere-based flow cytometric assays. Exp Hematol. 2002; 30 1227-1237
- 23 Knebel B, Janssen O E, Hahn S et al. Increased low grade inflammatory serum markers in patients with polycystic ovary syndrome (PCOS) and their relationship to PPARgamma gene variants. Exp Clin Endocrinol Diabetes. 2008; 116 481-486
- 24 Fain J N. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006; 74 443-477
- 25 Wong H L, Pfeiffer R M, Fears T R et al. Reproducibility and correlations of multiplex cytokine levels in asymptomatic persons. Cancer Epidemiol Biomarkers Prev. 2008; 17 3450-3456
- 26 Karadeniz M, Erdogan M, Zengi A et al. Polymorphism of the interleukin-10 gene in polycystic ovary syndrome. Int J Immunogenet. 2008; 35 119-123
- 27 Benson S, Janssen O E, Hahn S et al. Obesity, depression, and chronic low-grade inflammation in women with polycystic ovary syndrome. Brain Behav Immun. 2008; 22 177-184
- 28 Hoffman W H, Burek C L, Waller J L et al. Cytokine response to diabetic ketoacidosis and its treatment. Clin Immunol. 2003; 108 175-181
- 29 Zozulinska D, Majchrzak A, Sobieska M et al. Serum interleukin-8 level is increased in diabetic patients. Diabetologia. 1999; 42 117-118
- 30 Fontana L, Eagon J C, Colonna M et al. Impaired mononuclear cell immune function in extreme obesity is corrected by weight loss. Rejuvenation Res. 2007; 10 41-46
- 31 DeLeón-Navaa M A, Navaa K, Soldevilaa G et al. Immune sexual dimorphism: Effect of gonadal steroids on the expression of cytokines, sex steroid receptors, and lymphocyte proliferation. The Journal of Steroid Biochemistry and Molecular Biology. 2009; 113 57-64
- 32 González D A, Díaz B B, Rodríguez Pérez M del C et al. Sex hormones and autoimmunity. Immunol Lett. 2010; 133 6-13
- 33 Schneider C P, Schwacha M G, Samy T S et al. Androgen-mediated modulation of macrophage function after trauma-hemorrhage: central role of 5alpha-dihydrotestosterone. J Appl Physiol. 2003; 95 104-112
- 34 Escobar-Morreale H F. Polycystic ovary syndrome: treatment strategies and management. Expert Opin Pharmacother. 2008; 9 2995-3008
- 35 Luque-Ramírez M, Escobar-Morreale H F. Treatment of polycystic ovary syndrome (PCOS) with metformin ameliorates insulin resistance in parallel with the decrease of serum interleukin-6 concentrations. Horm Metab Res. 2010; 42 815-820
- 36 Daugherty A, Rateri D L. T lymphocytes in atherosclerosis. The Yin-Yang of Th1 and Th2 influence on lesion formation. Circ Res. 2002; 90 1039-1040
- 37 Laurat E, Poirier B, Tupin E et al. In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice. Circulation. 2001; 104 197-202
- 38 Pinderski L J, Fischbein M P, Subbanagounder G et al. Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient mice by altering lymphocyte and macrophage phenotypes. Circ Res. 2002; 90 1064-1071
- 39 Fisman E Z, Adler Y, Tenenbaum A. Biomarkers in cardiovascular diabetology: interleukins and matrixins. Adv Cardiol. 2008; 45 44-64
- 40 Čerkienė Z, Eidukaitė A, Usonienė A. Immune factors in human embryo culture and their significance. Medicina (Kaunas). 2010; 46 233-239
- 41 Saito S, Nakashima A, Shima T et al. Th1 / Th2 / Th17 and Regulatory T-Cell Paradigm in Pregnancy. American Journal of Reproductive Immunology. 2010; 63 601-610
- 42 Koh K K, Han S H, Quon M J. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J Am Coll Cardiol. 2005; 46 1978-1985
- 43 Maedler K, Sergeev P, Ris F et al. Glucose-induced beta cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 2002; 110 851-860
- 44 Mueller R, Lee M S, Sawyer S P et al. Transgenic expression of interleukin 10 in the pancreas renders resistant mice susceptible to low dose streptozotocin-induced diabetes. J Autoimmun. 1996; 9 151-158
- 45 Gallinelli A, Ciaccio I, Giannella L et al. Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome. Fertil Steril. 2003; 79 1365-1372
- 46 Szelachowska M, Kretowski A, Kinalska I. Decreased in vitro IL-4 and IL-10 production by peripheral blood in first degree relatives at high risk of diabetes type-I. Horm Metab Res. 1998; 30 526-530
- 47 Rabinovitch A, Suarez-Pinzon W L. Roles of cytokines in the pathogenesis and therapy of type 1 diabetes. Cell Biochem Biophys. 2007; 48 159-163
- 48 Daugherty A, Rateri D L, King V L. IL-5 links adaptive and natural immunity in reducing atherosclerotic disease. J Clin Invest. 2004; 114 317-319
- 49 Weitzmann M N, Roggia C, Toraldo G et al. Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J Clin Invest. 2002; 110 1643-1650
Dr. rer. nat. J. Kotzka
Institut für Klinische Biochemie und Pathobiochemie · Deutsches Diabetes Zentrum · Leibnitz Zentrum für Diabetes Forschung an der Heinrich-Heine-Universität Düsseldorf
Auf’m Hennekamp 65
40225 Düsseldorf
Deutschland
Email: jkotzka@ddz.uni-duesseldorf.de