title: Can apical periodontitis modify systemic levels of inflammatory markers? A systematic review and meta-analysis.
abstract: BACKGROUND
  This systematic review and meta-analysis investigated evidence to support whether apical periodontitis (AP) can modify the systemic levels of inflammatory markers (IM) in humans.
  
  
  METHODS
  The MEDLINE, Embase, Cochrane, and PubMed databases were searched between 1948 and 2012, with no language restriction. Additionally, the bibliography of all relevant articles and textbooks were manually searched. Based on inclusion and exclusion criteria, 2 reviewers independently rated the quality of each study based on the Newcastle-Ottawa Scale. The primary outcome variable for meta-analysis was determined by the serum levels of IMs in AP subjects versus healthy controls or in AP subjects before versus after treatment intervention.
  
  
  RESULTS
  Among the 531 initially identified articles, 20 comprised the final analysis. Thirty-one different IMs were analyzed, with immunoglobulin (Ig) A, IgM, IgG, and C-reactive protein (CRP) being the most commonly investigated. CRP, interleukin (IL)-1, IL-2, IL-6, asymmetrical dimethylarginine, IgA, IgG, and IgM were shown to be increased in patients with AP compared with controls in most studies. Meta-analyses showed that serum levels of IgA (P = .001), IgG (P = .04), and IgM (P < .00001) were increased in humans with AP compared with healthy controls and serum levels of CRP, IgA, IgE, IgG, and IgM were not significantly different between patients with AP before and after treatment (P > .05).
  
  
  CONCLUSIONS
  Available evidence is limited but consistent, suggesting that AP is associated with increased levels of CRP, IL-1, IL-2, IL-6, asymmetrical dimethylarginine, IgA, IgG, and IgM in humans. These findings suggest that AP may contribute to a systemic immune response not confined to the localized lesion, potentially leading to increased systemic inflammation.
authors.affiliation: School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Medical and Dental Center of the Military Police of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: endomax@gmail.com.
authors.forename: Maximiliano Schünke
authors.initials: MS
authors.lastname: Gomes
authors.forename: Trevor Charles
authors.initials: TC
authors.lastname: Blattner
authors.forename: Manoel
authors.initials: M
authors.lastname: Sant'Ana Filho
authors.forename: Fabiana Soares
authors.initials: FS
authors.lastname: Grecca
authors.forename: Fernando Neves
authors.initials: FN
authors.lastname: Hugo
authors.forename: Ashraf F
authors.initials: AF
authors.lastname: Fouad
authors.forename: Mark A
authors.initials: MA
authors.lastname: Reynolds
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D007155:Immunologic Factors / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology*; D007378:Interleukins / Q000097:blood; D010485:Periapical Periodontitis / Q000276:immunology*
chemical_list: D015415:Biomarkers; D007132:Immunoglobulin Isotypes; D007155:Immunologic Factors; D018836:Inflammation Mediators; D007378:Interleukins; D002097:C-Reactive Protein
keywords: Apical periodontitis; inflammation; meta-analysis; vascular diseases