Effect of anti-tumor necrosis factor-α polyclonal antibody on restenosis after balloon angioplasty in a rabbit atherosclerotic model

Inflammation has been postulated to contribute to restenosis after balloon angioplasty. Tumor necrosis factor (TNF)-α is a pleiotropic proinflammatory cytokine involved in many features of inflammation. We examined the tissue expression pattern of TNF-α and the inflammatory response to arterial injury, and the effects of a goat anti-rabbit-TNF-α polyclonal antibody on tissue TNF-α expression, inflammation and restenosis in a rabbit atherosclerotic model. At different time points following air dessication and subsequent balloon injury, fresh rabbit femoral artery tissues were homogenized and analyzed for TNF-α levels by quantitative TNF-α bioassay. Rabbits were treated with a goat anti-rabbit-TNF-α polyclonal antibody, Serum and tissue TNF-α neutralization, macrophage infiltration (as an indicator of inflammation), and neointimal areas were determined. Balloon angioplasty increased tissue TNF-α expression 100 000-fold over baseline, and this increase persisted over 6 days after arterial injury, serum anti-TNF-α antibody levels were sufficient to neutralize tissue TNF-α activity by 60–75%, macrophage infiltration was suppressed, but did not decrease the neointimal formation. These data indicate that tissue TNF-α levels were markedly increased after balloon angioplasty. Anti-TNF-α treatment was sufficient to neutralize tissue TNF-α activity, reduce inflammation, but did not inhibit neointimal formation following balloon angioplasty in a rabbit atherosclerotic model.