Prevention of experimental myointimal hyperplasia by immunomodulation

Abstract

Introduction: we have tested the hypothesis that treatment with a mycobacterial preparation that modulates the antibody response, would diminish restenosis in a rat angioplasty model. Materials/Methods: male Sprague-Dawley rats were used. All immunisations were given subcutaneously. Group A (control) received normal saline on days 0, 21, and 42. Group B received SRL172 on days 0, 21, and 42. Group C received SRL172 on days 0, 21, and 42, and hsp65/Incomplete Freund's on days 21 and 42. Group D received hsp65/ Freund's on days 21 and 42. Right common carotid arteries were balloon-injured on day 63 using a standard technique known to produce MIH and animals were sacrificed on day 77. For each carotid 6 μm cross sections were cut from paraffin blocks. Cross-sectional areas were measured by computerised planimetry. Results: balloon injury resulted in MIH in all animals. Data represents mean ± SEM for the percentage of area enclosed within the internal elastic lamina occupied by MIH (% MIH); which for groups A, B, C, and D was 85 ± 11, 24 ± 3, 27 ± 7, and 17 ± 3 respectively. All the treatment groups had significantly less MIH when compared to the control group but no statistically significant difference was found between any of the treatment groups. Conclusions: this is the first report that immunomodulation with mycobacterial material suitable for use in man, can reduce MIH. Since such modulation has low risk, this raises the prospect of an important new therapeutic modality to combat restenosis. © 2002 Harcourt Publishers Ltd.