Interleukin-7-mediated inflammation in unstable angina: possible role of chemokines and platelets.
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.


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-1alpha 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.
Damås
Jan Kristian
JK
Research Institute for Internal Medicine, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway.
Waehre
Torgun
T
Yndestad
Arne
A
Otterdal
Kari
K
Hognestad
Aina
A
Solum
Nils Olav
NO
Gullestad
Lars
L
Frøland
Stig S
SS
Aukrust
Pål
P
D000789:Angina, Unstable / Q000097:blood / Q000150:complications / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000378:metabolism*; D015851:Interleukin-7 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012016:Reference Values
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D015851:Interleukin-7; D019402:Macrophage Inflammatory Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D019707:Receptors, Chemokine; C082835:thrombin receptor peptide (42-47); D001241:Aspirin