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Inflammatory imbalance between IL-10 and TNFα in unstable angina potential plaque stabilizing effects of IL-10

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Abstract 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. Design

Plasma levels of tumour necrosis factor (TNF)α 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 TNFα 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 TNFα:IL-10 ratio, particularly in the unstable angina patients; (3) while exogenously added IL-10 markedly inhibited the release of TNFα, 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. Conclusion

Patients with unstable angina appear to have an imbalance between TNFα 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.

Keywords: Atherosclerosis; immunology; interleukin-10; matrix metalloproteinase; unstable angina

Document Type: Research Article


Affiliations: Rikshospitalet, Oslo, Norway

Publication date: 2002-11-01

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