PMID- 24956549
OWN - NLM
STAT- MEDLINE
DCOM- 20150129
LR  - 20211021
IS  - 1097-6868 (Electronic)
IS  - 0002-9378 (Print)
IS  - 0002-9378 (Linking)
VI  - 211
IP  - 6
DP  - 2014 Dec
TI  - Evidence of mononuclear cell preactivation in the fasting state in polycystic 
      ovary syndrome.
PG  - 635.e1-7
LID - S0002-9378(14)00624-3 [pii]
LID - 10.1016/j.ajog.2014.06.044 [doi]
AB  - 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. STUDY 
      DESIGN: Twenty women with PCOS (10 lean, 10 obese) and 20 weight-matched controls 
      (10 lean, 10 obese) volunteered for study participation. Tumor necrosis factor-alpha 
      (TNF-alpha) 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-alpha 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-alpha 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). CONCLUSION: 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.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Gonzalez, Frank
AU  - Gonzalez F
AD  - Department of Obstetrics and Gynecology, Indiana University School of Medicine, 
      Indianapolis, IN. Electronic address: gonzalef@iupui.edu.
FAU - Kirwan, John P
AU  - Kirwan JP
AD  - Department of PathoBiology, Lerner Research Institute, Cleveland Clinic, 
      Cleveland, OH.
FAU - Rote, Neal S
AU  - Rote NS
AD  - Department of Reproductive Biology, Case Western Reserve University School of 
      Medicine, Cleveland, OH.
FAU - Minium, Judi
AU  - Minium J
AD  - Department of Reproductive Biology, Case Western Reserve University School of 
      Medicine, Cleveland, OH.
LA  - eng
GR  - R03 HD048535/HD/NICHD NIH HHS/United States
GR  - UL1 TR000439/TR/NCATS NIH HHS/United States
GR  - HD-048535/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140620
PL  - United States
TA  - Am J Obstet Gynecol
JT  - American journal of obstetrics and gynecology
JID - 0370476
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Absorptiometry, Photon
MH  - Adult
MH  - Body Fat Distribution
MH  - Case-Control Studies
MH  - *Fasting
MH  - Female
MH  - Glucose Tolerance Test
MH  - Humans
MH  - In Vitro Techniques
MH  - Insulin Resistance
MH  - Interleukin-6/*immunology
MH  - Leukocytes, Mononuclear/drug effects/*immunology
MH  - Lipopolysaccharides/*pharmacology
MH  - Lymphocyte Activation/*immunology
MH  - Obesity/*immunology/metabolism
MH  - Polycystic Ovary Syndrome/*immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/drug effects/*immunology
MH  - Young Adult
PMC - PMC4253610
MID - NIHMS607211
OTO - NOTNLM
OT  - inflammation
OT  - lipopolysaccharide
OT  - mononuclear cell preactivation
COIS- DISCLOSURE STATEMENT: The authors report no conflict of interest.
EDAT- 2014/06/24 06:00
MHDA- 2015/01/30 06:00
PMCR- 2015/12/01
CRDT- 2014/06/24 06:00
PHST- 2014/04/22 00:00 [received]
PHST- 2014/06/10 00:00 [revised]
PHST- 2014/06/18 00:00 [accepted]
PHST- 2014/06/24 06:00 [entrez]
PHST- 2014/06/24 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - S0002-9378(14)00624-3 [pii]
AID - 10.1016/j.ajog.2014.06.044 [doi]
PST - ppublish
SO  - Am J Obstet Gynecol. 2014 Dec;211(6):635.e1-7. doi: 10.1016/j.ajog.2014.06.044. 
      Epub 2014 Jun 20.