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

J Gerontol A Biol Sci Med Sci. 2011 Apr;66(4):437-43. doi: 10.1093/gerona/glq225. Epub 2011 Feb 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Inflammation / blood*
  • Interleukin 1 Receptor Antagonist Protein / blood*
  • Interleukin-18 / blood
  • Interleukin-1beta / blood
  • Interleukin-6 / blood*
  • Italy
  • Longitudinal Studies
  • Lysine / analogs & derivatives*
  • Lysine / blood
  • Male
  • Middle Aged
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / blood*
  • Receptors, Interleukin-6 / blood
  • Transforming Growth Factor beta / blood
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-18
  • Interleukin-1beta
  • Interleukin-6
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Receptors, Interleukin-6
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • N(6)-carboxymethyllysine
  • Lysine