Hansson G K, Holm J
Department of Clinical Chemistry, Gothenburg University, Sweden.
Circulation. 1991 Sep;84(3):1266-72. doi: 10.1161/01.cir.84.3.1266.
Arterial injury initiates a proliferative response among the smooth muscle cells of the artery. This leads to the formation of a thickened intima that may reduce the diameter of the arterial lumen. Such intimal lesions often develop after vascular surgery and angioplastic procedures. Previous cell culture studies have shown that the lymphokine, interferon-gamma (gIFN), inhibits smooth muscle cell proliferation.
We therefore tested whether administration of exogenous gIFN could inhibit the development of intimal lesions. Rat carotid arteries were denuded with a balloon catheter, resulting in the formation of a standardized intimal lesion. The animals were then treated with recombinant rat gIFN at 200,000 units (approximately 400,000 units or 100 micrograms/kg body wt) administered parenterally once daily for 7 days. Autoradiographic analysis of 3H-thymidine incorporation revealed that gIFN reduced the early smooth muscle replication by approximately 75%. gIFN treatment for 1 week resulted in a 50% reduction of intimal cross-section area at 2 weeks after injury when compared to control rats injected with buffer alone. The difference in lesion development persisted in rats analyzed 10 weeks after injury, suggesting that proliferative events during the first week determine the long-term development of the intima. Inhibition of lesion development was accompanied by expression of the class II histocompatibility (Ia) gene, RT1B, suggesting that both were directly related to the administration of gIFN.
These results show that gIFN is a potent inhibitor of the formation of arterial proliferative lesions in vivo. It is possible that gIFN could be useful in preventing arterial stenosis after surgery and angioplasty in man.
动脉损伤会引发动脉平滑肌细胞的增殖反应。这会导致内膜增厚，进而可能减小动脉管腔的直径。此类内膜病变常在血管手术和血管成形术后发生。以往的细胞培养研究表明，淋巴因子γ干扰素（γIFN）可抑制平滑肌细胞增殖。
因此，我们测试了外源性γIFN的给药是否能抑制内膜病变的发展。用球囊导管剥脱大鼠颈动脉，从而形成标准化的内膜病变。然后，对动物进行重组大鼠γIFN治疗，剂量为200,000单位（约400,000单位或100微克/千克体重），每天经肠胃外给药一次，持续7天。对3H-胸腺嘧啶核苷掺入的放射自显影分析显示，γIFN使早期平滑肌复制减少了约75%。与仅注射缓冲液的对照大鼠相比，γIFN治疗1周后，损伤后2周时内膜横截面积减少了50%。在损伤后10周分析的大鼠中，病变发展的差异仍然存在，这表明第一周的增殖事件决定了内膜的长期发展。病变发展的抑制伴随着II类组织相容性（Ia）基因RT1B的表达，表明两者均与γIFN的给药直接相关。
这些结果表明，γIFN是体内动脉增殖性病变形成的有效抑制剂。γIFN有可能用于预防人类手术后和血管成形术后的动脉狭窄。
