Inflammatory imbalance between IL-10 and TNFalpha in unstable angina potential plaque stabilizing effects of IL-10.
BACKGROUND
The pathogenesis of atherosclerosis and acute coronary syndromes involves inflammation and immunological mechanisms. We hypothesized that patients with unstable angina may have an imbalance between inflammatory and anti-inflammatory cytokines.


METHODS
Plasma levels of tumour necrosis factor (TNF)alpha and interleukin (IL)-10 were analyzed in 44 patients with stable angina, 29 patients with unstable angina and 20 controls. mRNA levels of these cytokines were analyzed in peripheral blood mononuclear cells (PBMC). We also studied the in vitro effects of IL-10 in PBMC from unstable angina patients.


RESULTS
Our main findings were: (1) the angina patients and particularly those with unstable disease had significantly raised TNFalpha in comparison with the controls, both at the protein and mRNA level; (2) in contrast, the levels of IL-10 were not different in the angina patients in comparison with the healthy controls, resulting in a markedly enhanced TNFalpha:IL-10 ratio, particularly in the unstable angina patients; (3) while exogenously added IL-10 markedly inhibited the release of TNFalpha, IL-8 and tissue factor as well as impairing the gelatinolytic activity and mRNA production of matrix metalloproteinase-9, it enhanced the tissue inhibitor of this metalloproteinase (i.e. TIMP-1) in PBMC from the unstable angina patients.


CONCLUSIONS
Patients with unstable angina appear to have an imbalance between TNFalpha and IL-10, possibly favouring inflammatory net effects. IL-10 may have beneficial effects on mechanisms that are important in plaque rupture and thrombus formation.
Waehre
T
T
Research Institute for Internal Medicine, Rikshospitalet, Oslo, Norway. torgun.wahre@klinmed.uio.no
Halvorsen
B
B
Damås
J K
JK
Yndestad
A
A
Brosstad
F
F
Gullestad
L
L
Kjekshus
J
J
Frøland
S S
SS
Aukrust
P
P
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy; D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013268:Stimulation, Chemical; D013925:Thromboplastin / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
D016209:Interleukin-8; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013925:Thromboplastin; D020780:Matrix Metalloproteinase 9