Interleukin 8 serum levels and the risk of myocardial infarction. Results from the Stockholm Heart Epidemiology program

Abstract

Since its discovery during the late 80s, a large body of evidence suggests a key role of interleukin 8 (IL8) in the natural history of atherosclerosis from the early stages of vascular inflammation to the remodeling after myocardial infarction (MI). The aim of the present study was to evaluate the association of IL8 serum levels with the risk of MI in men and women from the Stockholm Heart Epidemiology Program (SHEEP), a case-control population with 2774 subjects (cases n=1213 and controls n=1561). Cases were identified as patients having been diagnosed with a non-fatal MI and controls were sex and age-matched subjects. Blood samplings were performed at least three months after the MI. IL8 (pg/ml) was measured in serum samples from 1133 controls and 714 cases using the Meso Scale Discovery's Multi-Array. IL8 serum levels were divided in quartiles according to IL8 distribution in controls (Q1≤ 8.3, Q2>8.3≤13.6, Q3>13.6≤20.9, Q4>20.9) In women, serum IL8 levels were higher in controls 14.2 (8.7-22.1) than in cases 11.6 (6.6-18.0) p= 0.0002 and strongly related to a protective effect of first time MI. Women with IL8 serum levels in the highest quartile (Q4) had an unadjusted OR of 0.44 (95% CI, 0.3-0.7), as compared to women exposed to low IL8 (Q1). Adjustments by insulin, BMI and CRP (OR [95% CI] = 0.41 [0.2-0.7]) and additional adjustment for the traditional cardiovascular risk factors (OR [95% CI] = 0.35 [0.2-0.6]) and by drug therapy (OR [95% CI] = 0.37 [0.2-0.8]) did not significantly change the risk estimates. In men serum levels of IL8 were higher in controls than in cases and associated with a reduced, however non-significant, MI risk. We report the largest investigation performed so far on the association between IL8 serum levels and the risk of MI. Our data demonstrates that in women high IL8 serum levels are associated with a reduced risk of MI. This may reflect a shift in the IL-8 properties during the different stages of the atherosclerotic process from a pro-inflammatory to an anti-inflammatory, pro-angiogenetic cytokine.