title: Investigation of systemic inflammatory response in first trimester pregnancy failure.
abstract: BACKGROUND
  The contribution of local and systemic inflammation to the pathophysiology of sporadic first trimester miscarriages remains unclear. The objective of this study was to investigate the inflammatory response in the circulation of women presenting with first trimester miscarriage.
  
  
  METHODS
  Levels of tumour necrosis factor alpha (TNFα), TNF receptors 1 and 2, interferon gamma (IFNγ), interleukin (IL)-6 and IL-10 were assayed using cytometric bead arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35 normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow cytometry was carried out with samples from 17 euploid and 16 aneuploid miscarriages, 18 pregnant controls and 13 NPW.
  
  
  RESULTS
  The plasma of women with euploid miscarriage contained significantly higher circulating levels of TNFα (P < 0.005), IFNγ (P < 0.005), IL-6 (P < 0.005) and IL-10 (P < 0.01) than that of pregnant controls, irrespective of gestational age. Significantly (P < 0.05) higher TNF-R1 levels at 6-9 weeks, and significantly higher TNFα/IL-6 (P < 0.001) and significantly lower TNFα/IL-10 (P < 0.001) and IFNγ/IL-10 (P < 0.001) ratios at 10-14 weeks, were also found in euploid miscarriage cases compared with pregnant controls. TNFα/IL-10 ratio in plasma was significantly (P < 0.05) lower in miscarriages with an abnormal karyotype than those with normal karyotype. Normal pregnant women had a significantly higher plasma level of IFNγ (P < 0.01) and IFNγ/IL-10 ratio (P < 0.005), a significantly (P < 0.005) lower TNF-R1 level, and a significant (P < 0.05) increase in stimulated TNFα in monocytes, compared with NPW.
  
  
  CONCLUSIONS
  Our data confirm that there is an inflammatory reaction in normal pregnancy compared with the non-pregnant state, which may be disrupted during miscarriage.
authors: Academic Department of Obstetrics and Gynaecology, UCL Institute for Women' s Health, University College London, 86-96, Chenies Mews, London WC1E 6HX, UK. jean.calleja-agius@um.edu.mt
authors: J
authors: J
authors: Calleja-Agius
authors: E
authors: E
authors: Jauniaux
authors: A R
authors: AR
authors: Pizzey
authors: S
authors: S
authors: Muttukrishna
mesh_terms: D000030:Abortion, Missed / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000276:immunology; D000022:Abortion, Spontaneous / Q000097:blood / Q000235:genetics / Q000276:immunology*; D000782:Aneuploidy; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000503:physiopathology*; D011261:Pregnancy Trimester, First; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood / Q000737:chemistry; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000737:chemistry; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506235:TNFRSF1A protein, human; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha