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

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, CM L, interleukin-1 receptor antagonist (IL-IRA), 1L-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-6 receptor (IL-6R), IL-18, C-reactive protein (CRP), transforming growth factor-beta (TGF-beta), and fibrinogen were measured. Results. Log plasma esRAGE was associated with log IL-IRA (beta = -0.069, SE = 0.036, p = .05) and log IL-6 (beta = 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-beta but did not reach statistical significance (beta = -0.091, SE = 0.053, p =.09). Log plasma esRAGE was not significantly associated with log IL-1 beta, log TNF-alpha, IL-6R, log IL-18, or CRP. Log plasma CML was not associated with any of the inflammatory mediators except for IL-6R (beta = -14.10, SE = 5.94, p = .02) and fibrinogen (beta = 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-IRA. These findings suggest that plasma esRAGE plays a role in modulating inflammation, although the exact mechanisms remain to be elucidated.