The Intricacies of Inflammation
How does the process of inflammation play a role in cardiovascular and autoimmune diseases?
As the body’s response to damaging events, inflammation is marked by Interleukin-1, which plays a central role in regulating the body's inflammatory response by initiating a series of signals. Whereas acute inflammation is often necessary as a protective defense against infection and other insults, unchecked, chronic inflammation is implicated in autoimmune diseases.
To study the genetic variants that produce inhibition of Interleukin-1, the Interleukin-1 Genetics Consortium developed a genetic score to combine the effects of variants, assessing the effect of this score on key biological indicators of inflammation. The researchers found that individuals who carried the genetic variants (displaying naturally-occurring interleukin-1 inhibition) showed a decreased risk of developing rheumatoid arthritis (an autoimmune disease).
Blocking interleukin-1 increased an individual's risk of developing coronary heart disease: the risk of a heart attack was 15% higher in people who inherited a greater tendency to block interleukin-1. Further, blocking interleukin-1 also increased an individual's risk of developing abdominal aortic aneurysm.
The study authors submit that: “Human genetic data suggest that long-term dual [interleukin-1 alpha/beta] inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis.”
The Interleukin 1 Genetics Consortium. “Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis.” Lancet Diabetes Endocrinol. 2015 Feb 25.