Studies in vitro have suggested that inflammatory cytokines may play an important role in the pathogenesis of atherosclerosis. However, little is known about their effects in vivo. Thus, the present study was designed to determine in vivo what histological and functional changes may be induced by chronic treatment with IL-1β, one of the major inflammatory cytokines, and also to clarify what mechanisms are involved in those changes. Under aseptic conditions, proximal segments of the left porcine coronary arteries were gently wrapped with cotton mesh absorbing Sepharose beads either with or without recombinant human IL-1β. From 1 to 4 wk after the operation, coronary vasospastic responses to intracoronary serotonin or histamine were noted at the IL-1β-treated site but not at the control site. Histologically, intimal thickening was greater at the 1L-1β-treated site than at the control site. Those functional and histological changes induced by the chronic treatment with IL-1β were significantly inhibited by the simultaneous treatment with a neutralizing antibody to either IL-1β or PDGF. These results indicate that chronic treatment with IL-1β induces coronary intimal lesions and vasospastic responses in porcine coronary arteries in vivo and also suggest that these changes are substantially mediated by PDGF.
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