Published Online
on May 12, 2003

A more recent version of this article appeared on June 3, 2003

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Submitted on February 5, 2003
Accepted on February 28, 2003

Interleukin-7-Mediated Inflammation in Unstable Angina. Possible Role of Chemokines and Platelets

Jan Kristian Damås MD, PhD, Torgun Wæhre MD, Arne Yndestad MSc, Kari Otterdal MSc, Aina Hognestad MD, Nils Olav Solum PhD, Lars Gullestad MD, PhD, Stig S. Frøland MD, PhD, and Pål Aukrust MD, PhD^*

From Research Institute for Internal Medicine (J.K.D., T.W., A.Y., K.O., A.H., N.O.S., S.S.F., P.A.), the Department of Cardiology (J.K.D., T.W., A.H., L.G.), Section of Clinical Immunology and Infectious Diseases (S.S.F., P.A.), Rikshospitalet, Oslo, Norway.

^* To whom correspondence should be addressed. E-mail: pal.aukrust{at}rikshospitalet.no.

Background--Atherogenesis and plaque destabilization involve immune-mediated mechanisms, but the actual mediators have not been fully clarified. Interleukin (IL)-7 is a regulator of T-cell homeostasis but also may be involved in inflammation. We hypothesized that IL-7 could be involved in the inflammatory processes observed in atherosclerosis and acute coronary syndromes.

Methods and Results--To study the role of IL-7 in coronary artery disease, we analyzed IL-7 levels and the effect of this cytokine on inflammatory mediators in patients with stable and unstable angina and in healthy control subjects. Our major findings were (1) Plasma levels of IL-7 were significantly increased in patients with stable (n=30) and unstable angina (n=30) comparing healthy control subjects (n=20), particularly in those with unstable disease. (2) Increased release from activated platelets appeared to be a major contributor to the raised IL-7 levels in patients with angina. (3) IL-7 enhanced the expression of several inflammatory chemokines in peripheral blood mononuclear cells from both healthy control subjects and patients with angina, particularly in those with unstable disease. Similar effects were seen in monocytes but not in T cells. (4) MIP-1 further increased the release of IL-7 from platelets in a dose-dependent manner. (5) Aspirin reduced both the spontaneous and the SFLLRN-stimulated release of IL-7 from platelets, and when administered to healthy control subjects for 7 days (160 mg qd), it reduced plasma levels of IL-7.

Conclusions--Our findings suggest a role for IL-7-driven inflammation in atherogenesis and the promotion of clinical instability in coronary artery disease involving interactions between platelets, monocytes, and chemokines.

Key words: angina • immunology • inflammation • platelets

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