title: Endogenous secretory receptor for advanced glycation end products is associated with low serum interleukin-1 receptor antagonist and elevated IL-6 in older community-dwelling adults.
abstract: BACKGROUND
  Advanced glycation end products (AGEs) are thought to cause inflammation through interaction with the receptor for AGEs (RAGE), therefore contributing to adverse aging-related processes. The relationship between AGEs, RAGE, and inflammation has not been well characterized.
  
  
  METHODS
  We examined the relationship of plasma endogenous secretory RAGE (esRAGE); carboxymethyl-lysine (CML), a circulating AGE; and inflammatory mediators in 1,298 adults, 20-97 years, who participated in the InCHIANTI study in Tuscany, Italy. Blood levels of esRAGE, CML, interleukin-1 receptor antagonist (IL-1RA), IL-1β, tumor necrosis factor-α (TNF-α), IL-6, IL-6 receptor (IL-6R), IL-18, C-reactive protein (CRP), transforming growth factor-β (TGF-β), and fibrinogen were measured.
  
  
  RESULTS
  Log plasma esRAGE was associated with log IL-1RA (β = -0.069, SE = 0.036, p = .05) and log IL-6 (β = 0.077, SE = 0.035, p = .03), respectively, in separate multivariable linear regression models, adjusting for potential confounders. Log plasma esRAGE was also negatively associated with log TGF-β but did not reach statistical significance (β = -0.091, SE = 0.053, p = .09). Log plasma esRAGE was not significantly associated with log IL-1β, log TNF-α, IL-6R, log IL-18, or CRP. Log plasma CML was not associated with any of the inflammatory mediators except for IL-6R (β = -14.10, SE = 5.94, p = .02) and fibrinogen (β = 13.95, SE = 7.21, p = .05) in separate multivariable models, adjusting for potential confounders.
  
  
  CONCLUSIONS
  Plasma esRAGE is correlated with higher IL-6 and lower IL-1RA. These findings suggest that plasma esRAGE plays a role in modulating inflammation, although the exact mechanisms remain to be elucidated.
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Smith Building M015, 400 N. Broadway, Baltimore, MD 21287, USA.
authors.forename: Candace L
authors.initials: CL
authors.lastname: Crasto
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Mansi
authors.initials: M
authors.lastname: Dalal
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Corsi
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007558:Italy; D008137:Longitudinal Studies; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D019947:Receptors, Interleukin-6 / Q000097:blood; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C048496:N(6)-carboxymethyllysine; D008239:Lysine