title: Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas.
abstract: BACKGROUND
  Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas.
  
  
  METHODS
  This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa.
  
  
  RESULTS
  Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6).
  
  
  CONCLUSIONS
  These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of colorectal adenomas.
authors: Center for Gastrointestinal Biology and Disease, University of North Carolina, 103 Mason Farm Road, 7340 Medical Biomolecular Research Building, CB # 7032, 27599-7032, Chapel Hill, NC 27599, USA. melissa_kang@med.unc.edu
authors: Melissa
authors: M
authors: Kang
authors: Patrick
authors: P
authors: Edmundson
authors: Felix
authors: F
authors: Araujo-Perez
authors: Amber N
authors: AN
authors: McCoy
authors: Joseph
authors: J
authors: Galanko
authors: Temitope O
authors: TO
authors: Keku
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis*; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004731:Endotoxins; D012333:RNA, Messenger