title: Evidence of mononuclear cell preactivation in the fasting state in polycystic ovary syndrome.
abstract: OBJECTIVE
  We evaluated mononuclear cell (MNC) preactivation in women with polycystic ovary syndrome (PCOS) by examining the effect of in vitro lipopolysaccharide (LPS) exposure on cytokine release in the fasting state.
  
  
  METHODS
  Twenty women with PCOS (10 lean, 10 obese) and 20 weight-matched controls (10 lean, 10 obese) volunteered for study participation. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release was measured from mononuclear cells isolated from fasting blood samples and cultured in the presence and absence of LPS. Plasma IL-6 was measured from the same fasting blood samples. Insulin sensitivity was derived from an oral glucose tolerance test using the Matsuda index, and truncal fat was measured by dual-energy x-ray absorptiometry.
  
  
  RESULTS
  The percent change from baseline in TNF-α and IL-6 release from MNC following LPS exposure was increased (P < .04) in lean and obese women with PCOS and obese controls compared with lean controls. Plasma IL-6 was increased (P < .02) in obese women with PCOS compared with lean women with PCOS, which in turn was increased (P < .02) compared with lean controls. The MNC-derived TNF-α and IL-6 responses from MNCs were negatively correlated with insulin sensitivity (P < .03) and positively correlated with testosterone (P < .03) and androstenedione (P < .006) for the combined groups. Plasma IL-6 was positively correlated with percentage truncal fat (P < .008).
  
  
  CONCLUSIONS
  In PCOS, increased cytokine release from MNCs following LPS exposure in the fasting state reveals the presence of MNC preactivation. Importantly, this phenomenon is independent of obesity and may contribute to the development of insulin resistance and hyperandrogenism in PCOS. In contrast, the source of plasma IL-6 elevations in PCOS may be excess adiposity.
authors: Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN. Electronic address: gonzalef@iupui.edu.
authors: Frank
authors: F
authors: González
authors: Department of PathoBiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors: John P
authors: JP
authors: Kirwan
authors: Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH.
authors: Neal S
authors: NS
authors: Rote
authors: Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH.
authors: Judi
authors: J
authors: Minium
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D050218:Body Fat Distribution; D016022:Case-Control Studies; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D066298:In Vitro Techniques; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009765:Obesity / Q000276:immunology* / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
keywords: inflammation; lipopolysaccharide; mononuclear cell preactivation