Cytokine Levels Tied to Unhealthy Aging
Published: Sep 17, 2013 | Updated: Sep 17, 2013
By Kristina Fiore, Staff Writer, MedPage Today

Full Story:  http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/41662

Chronically elevated levels of interleukin-6 (IL-6) were associated with unhealthy aging and a higher risk of cardiovascular events and death, researchers found.

In an analysis of data from the Whitehall II study, patients with high levels of the inflammatory cytokine were significantly less likely to fit a profile of healthy aging — including being free of chronic disease and having optimal physical and mental functioning — over 10 years (odds ratio 0.45, 95% CI 0.35-0.59), reported Tasnime Akbaraly, PhD, of the Institut National de la Sante et de la Recherche Medicale in Montpellier in France, and colleagues.

“We found that high IL-6 levels at baseline were associated with lower odds of good cardiovascular, respiratory and musculoskeletal functioning and good mental well-being, as well as lower odds of remaining free of diabetes and disability,” they wrote online in CMAJ.

“If confirmed, these results shed new light on the importance of assessing long-term chronic inflammation in geriatric clinical practice, not only to target individuals at risk of unhealthy aging but also to promote ideal health by managing long-term chronic inflammation,” the authors added.

Much research has pointed to chronic inflammation as a major driver of age-related diseases, and has suggested that IL-6 is a key player in that association. Recent work has suggested that the inflammatory cytokine drives downstream inflammatory markers such as C-reactive protein and fibrinogen.

To assess its role in various aging phenotypes, Akbaraly and colleagues assessed 3,044 middle-aged patients (28% women) from the Whitehall II study, which was conducted among public servants in the U.K.

None of these patients had any history of stroke, myocardial infarction, or cancer when they were enrolled at baseline (1997-1999) and the researchers measured inflammatory markers twice — once at baseline and once 5 years prior to baseline (1991-1993).

At the end of a 10-year follow-up period, the researchers placed patients into one of four aging phenotypes:

• Successful aging (23.7%)
• Fatal or nonfatal cardiovascular disease events (10.6%)
• Death from noncardiovascular causes (4.8%)
• Normal aging (60.9%)

The researchers found that overall, successful agers were more likely to have low levels of IL-6 at baseline, while those with cardiovascular events, or who died from noncardiovascular, causes were more likely to have high levels of the cytokine (P<0.001).

In adjusted analyses, patients with high levels of IL-6 at baseline were significantly less likely than those with low levels to achieve successful aging over a decade. These patients were also at increased risk of cardiovascular events (OR 1.76, 95% CI 1.21-2.55) and death from a noncardiovascular cause (OR 2.64, 95% CI 1.53-4.55) during the study period.

Akbaraly and colleagues also found in adjusted analyses that having high IL-6 readings (above 2.0 ng/L) twice over the study period nearly halved the odds of successful aging over 10 years (OR 0.53, 95% CI 0.38-0.74, P<0.001).

Having two high readings also increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15-2.33, P=0.002) and of noncardiovascular death (OR 2.43, 95% CI 1.58-3.80,P<0.001), they reported.

Finally, high levels of IL-6 lowered the odds of remaining free of diabetes (OR 0.35, 95% CI 0.24-0.51, P<0.001 for trend).

These results suggest that “measuring chronic inflammation twice may be a better predictor of future cardiovascular disease and noncardiovascular death than measuring inflammation only once,” they wrote.

The study was limited by a potential lack of generalizability outside of the middle-age London-based civil servants enrolled in the study, and also by its observational nature.

But the researchers still concluded that chronic inflammation is related to unhealthy aging, and that maintaining low levels of IL-6 “may facilitate successful aging by reducing the likelihood of impaired respiratory and musculoskeletal functioning, and increasing the likelihood of remaining free of diabetes.”