An inflammatory pathway of IFN-gamma production in coronary atherosclerosis

H Ranjbaran, Si Sokol, A Gallo, Re Eid, Ao Iakimov, Alessio D'Alessio, Jr Kapoor, S Akhtar, Cj Howes, M Aslan, S Pfau, Js Pober, G. Tellides

Risultato della ricerca: Contributo in rivistaArticolo in rivista

77 Citazioni (SciVal)


Inflammation is associated with the pathogenesis of coronary atherosclerosis, although the mechanisms remain unclear. We investigated whether cytokine secretion by innate immune responses could contribute to the production of proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis. Cytokines were measured by ELISA in the plasma of patients with coronary atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all subjects, whereas a subset of patients demonstrated a coordinated induction of other IFN-gamma-related cytokines. Specifically, elevated plasma levels of IL-12 correlated with that of IFN-gamma and IFN-gamma-inducible chemokines, defining an IFN-gamma axis that was activated independently of IL-6 or C-reactive protein. Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels of the IFN-gamma axis, but not that of IL-18. Activation of the IFN-gamma axis was not associated with acute coronary syndromes, but portended increased morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other monokines, elicited secretion of IFN-gamma and IFN-gamma-inducible chemokines in human atherosclerotic coronary arteries maintained in organ culture. T cells were the principal source of IFN-gamma in response to IL-12/IL-18 within the arterial wall. This inflammatory response did not require, but was synergistic with and primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine-producing, nonproliferating, and noncytolytic phenotype, consistent with previous descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL-12/IL-18-dependent IFN-gamma secretion was prevented by a p38 MAPK inhibitor and not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic link between inflammation and Th1-type cytokine production in coronary atherosclerosis.
Lingua originaleEnglish
pagine (da-a)592-604
Numero di pagine13
RivistaJournal of Immunology
Stato di pubblicazionePubblicato - 2007


  • Coronary Artery Disease
  • Cytokines
  • Humans
  • Interferon-gamma
  • Interleukin-12
  • Interleukin-18
  • Th1 Cells


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