Immunotherapy for the Prevention of Myointimal Hyperplasia After Experimental Balloon Injury of the Rat Carotid Artery

Abstract

We assessed the effect of novel immunotherapeutic heat-killed bacterial (Actinomycetales) preparations on the development of myointimal hyperplasia (MIH) in a rat carotid balloon trauma model and the effect on the immune response by measuring the expression of interferon γ (IFN-γ; (Th1) and interleukin 4 (IL-4; Th2). There was a significant reduction (P < .001) in intima/media ratios (mean ± SEM) in the rats treated by immunomodulation (0.52 ± 0.03 Gordonia bronchialis, 0.60 ± 0.03 Rhodococcus coprophilus, 0.43 ± 0.03 Tsukamurella inchonensis, 0.37 ± 0.03 Mycobacterium vaccae), in comparison with untreated controls (0.91 ± 0.05). Postballoon trauma G bronchialis increased messenger RNA (mRNA) IFN-γ (P < .02) and reduced mRNA IL-4 (P < .05). R coprophilus, T inchonensis, and M vaccae significantly increased production of mRNA IFN-γ (P < .001). R coprophilus and M vaccae also decreased production of mRNA IL-4 (P < .05, P < .01). Treatment with heat-killed Actinomycetales inhibits MIH through a combination of enhanced Th1 and attenuated Th2 response. Immunomodulation may provide a novel therapeutic option to prevent restenosis.