Granstein R D, Rook A, Flotte T J, Haas A, Gallo R L, Jaffe H S, Amento E P
Wellman Laboratories, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Arch Dermatol. 1990 Oct;126(10):1295-302.
Interferon-gamma (IFN-gamma) suppresses the synthesis of collagen by fibroblasts in vitro and the synthesis of collagen in vivo in animal models. Therefore, recombinant human IFN-gamma was examined for its ability to clinically modify keloids. Subjects were treated by injection of either 0.01 or 0.1 mg of recombinant human IFN-gamma into one lesional site and diluent alone into another lesional site three times per week for 3 weeks. Keloids were measured and photographed before beginning therapy and weekly thereafter. Three days after the final injection, biopsies were performed on treated and control sites. Six of eight subjects who finished the course of treatment demonstrated reduction in size at the treated site with an average reduction in height of 30.4% vs 1.1% for control sites. Lesions treated with recombinant human IFN-gamma demonstrated alterations in both the epidermis and dermis. The epidermis showed thinning of the suprapapillary plates, compact hyperkeratosis, focal or diffuse parakeratosis, exocytosis of lymphocytes, and an increased quantity of mucin. The dermis contained a diminished quantity of thickened collagen bundles and active fibroblasts and an increased number of inflammatory cells and quantity of mucin. These results suggest the feasibility of using IFN-gamma in the treatment of abnormal fibrosis. Dose-ranging studies are required to establish whether IFN-gamma can fulfill a true clinical need in the treatment of keloidal scarring.
γ干扰素(IFN-γ)在体外可抑制成纤维细胞胶原蛋白的合成,在动物模型中也能抑制体内胶原蛋白的合成。因此,对重组人γ干扰素在临床上改善瘢痕疙瘩的能力进行了研究。受试者分别在一个皮损部位注射0.01毫克或0.1毫克重组人γ干扰素,在另一个皮损部位注射稀释剂,每周3次,共3周。在开始治疗前及之后每周对瘢痕疙瘩进行测量和拍照。最后一次注射3天后,在治疗部位和对照部位进行活检。完成治疗疗程的8名受试者中有6名在治疗部位的大小有所减小,治疗部位高度平均减小30.4%,而对照部位为1.1%。用重组人γ干扰素治疗的皮损在表皮和真皮均出现改变。表皮显示乳头上方板变薄、致密性角化过度、局灶性或弥漫性角化不全、淋巴细胞外渗以及黏蛋白量增加。真皮中增厚的胶原束和活跃的成纤维细胞数量减少,炎症细胞数量和黏蛋白量增加。这些结果提示使用γ干扰素治疗异常纤维化具有可行性。需要进行剂量范围研究以确定γ干扰素在治疗瘢痕疙瘩性瘢痕方面是否能真正满足临床需求。