title: Association between periodontitis and hyperlipidemia: cause or effect?
abstract: BACKGROUND
  Epidemiological studies suggest a relationship between periodontitis and coronary artery disease, but the mechanism has not been established. Recent studies in animals indicate that low dose endotoxin, as in a gram-negative infection, can induce hyperlipidemia and myeloid cell hyperactivity. The association between periodontitis, systemic exposure to Porphyromonas gingivalis, lipopolysaccharides (LPS), and hyperlipidemia has not been examined in humans.
  
  
  METHODS
  Sera were obtained from 26 adult periodontitis patients and 25 healthy control (C) subjects selected from patients and staff. Serum antibodies against Porphyromonas gingivalis and its LPS were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. Serum triglycerides (TG) and cholesterol (CHOL) were assayed by a commercial laboratory. The associations between AP and blood levels of TG, CHOL, and anti-P. gingivalis whole cells and LPS were examined by logistic regression analysis. Peripheral blood polymorphonuclear leukocytes (PMNs) from 6 healthy fasted donors were incubated with purified TG (0.1 mg/ml) for 2 hours at 37 degrees C, stimulated with 100 ng/ml P. gingivalis LPS, and the release of IL-1beta measured by ELISA.
  
  
  RESULTS
  The presence of periodontitis was significantly associated with age (odds ratio = 3.5, P = 0.04), elevated TG levels (odds ratio = 8.6, P = 0.0009), elevated CHOL levels (odds ratio = 7, P = 0.004), elevated ELISA titer (odds ratio = 35, P = 0.003) and reactivity with P. gingivalis LPS (odds ratio = 41, P = 0.001). PMNs from all 6 healthy patients released modest levels of IL-1beta (10 to 60 pg/ml) when stimulated with 100 ng/ml P. gingivalis LPS. Addition of TG resulted in a significant increase (P <0.05) in IL- 1beta secreted that ranged from 7 to 150% over LPS alone. No IL-1beta was elicited by TG or vehicle alone.
  
  
  CONCLUSIONS
  The results of this study indicate the presence of a significant relationship between periodontitis, hyperlipidemia, and serum antibodies against P. gingivalis LPS that warrants further examination in a larger patient population. Furthermore, these studies indicate that elevated triglycerides are able to modulate IL-1beta production by PMNs stimulated with P. gingivalis LPS.
authors.affiliation: Department of Periodontics and Biomedical Sciences, Baylor College of Dentistry, Dallas, TX 75266-0677, USA. ccutler@tambcd.edu
authors.forename: C W
authors.initials: CW
authors.lastname: Cutler
authors.forename: E A
authors.initials: EA
authors.lastname: Shinedling
authors.forename: M
authors.initials: M
authors.lastname: Nunn
authors.forename: R
authors.initials: R
authors.lastname: Jotwani
authors.forename: B O
authors.initials: BO
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Nares
authors.forename: A M
authors.initials: AM
authors.lastname: Iacopino
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications* / Q000382:microbiology; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D016017:Odds Ratio; D010518:Periodontitis / Q000150:complications* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology / Q000502:physiology; D014280:Triglycerides / Q000097:blood
chemical_list: D000907:Antibodies, Bacterial; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014280:Triglycerides; D002784:Cholesterol