Role of cytokines in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty

Background: Inflammatory cytokines play an important role in mediating inflammatory/proliferative responses including atherosclerosis. However, their role in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains to be clarified. Objective: To determine plasma levels of inflammatory cytokines as well as cytokine-generation capacities of monocytes before PTCA and after the follow-up period. Methods: Plasma levels of cytokines in 34 consecutive patients before and 3-6 months after PTCA were measured by enzyme-linked immunosorbent assay. We measured the plasma levels of macrophage-colony-stimulating factor (MCSF) and transforming growth factor-β. Cytokine-generation capacities of monocytes were also measured by a whole-blood induction method with lipopolysaccharide. The levels of cytokines measured for assessment of the capacities included those of interleukin-1α, interleukin-1β, interleukin-6, granulocyte-colony-stimulating factor, tumor necrosis factor-α and interferon-γ. Results: Plasma levels of MCSF in patients without restenosis (n = 20) decreased significantly (from 1460 ± 138 μg/ml before PTCA to 1039 ± 125 μg/ml after the follow-up period, P < 0.01), whereas those in patients with restenosis (n = 14) increased significantly (from 1107 ± 105 μg/ml before PTCA to 1039 ± 125 μg/ml after the follow-up period, P < 0.05). We noted a positive correlation between the increase in plasma levels of MCSF and the extent of loss of lumen by restenosis. Cytokine-generation capacities of monocytes for interleukin-1α and interleukin-1β of patients with restenosis significantly increased but those of patients without restenosis did not. Furthermore, plasma levels of C-reactive protein decreased significantly only in patients without restenosis after the follow-up period. Conclusions: These results suggest that inflammatory changes mediated by cytokines may be involved in the pathogenesis of restenosis after PTCA.