Harmon C S, Nevins T D
Hoffmann-La Roche Inc., Nutley, NJ 07110.
Lymphokine Cytokine Res. 1993 Aug;12(4):197-203.
In this study we have used a recently developed human hair follicle whole-organ culture system to investigate the effect of IL-1 alpha on hair follicle growth and hair fiber production. In the presence of 10 ng/ml IL-1 alpha, the growth of cultured human hair follicles ceased within 2-4 days, whereas control hair follicles grew for a period of 7-10 days. IL-1 alpha also inhibited hair fiber growth, but with an onset which occurred 3 days later than that of follicle growth inhibition. An IC50 value of approximately 30 pg/ml was obtained for IL-1 alpha inhibition of follicle growth. Incubation of hair follicles with IL-1 alpha resulted in a rapid, transient reduction in the rate of whole-follicle DNA synthesis. 1000-fold molar excess of IL-1 receptor antagonist prevented IL-1-induced follicle growth inhibition, while antagonist alone was without effect. The selective PKC inhibitor, Ro 31-7549, augmented IL-1-induced inhibition of hair follicle growth, but did not itself affect hair follicle growth. These findings indicate that IL-1 alpha exerts a rapid antiproliferative effect on hair follicles, and that inhibition of hair fiber growth is a secondary response. Thus, IL-1 may play a role in the pathophysiology of inflammatory hair loss conditions, such as alopecia areata, through a direct growth-inhibitory effect on hair follicles.
在本研究中,我们使用了最近开发的人毛囊全器官培养系统来研究白细胞介素-1α(IL-1α)对毛囊生长和毛发纤维生成的影响。在存在10 ng/ml IL-1α的情况下,培养的人毛囊生长在2-4天内停止,而对照毛囊生长7-10天。IL-1α也抑制毛发纤维生长,但其起效时间比毛囊生长抑制晚3天。IL-1α抑制毛囊生长的IC50值约为30 pg/ml。用IL-1α孵育人毛囊导致全毛囊DNA合成速率迅速、短暂降低。1000倍摩尔过量的IL-1受体拮抗剂可防止IL-1诱导的毛囊生长抑制,而单独的拮抗剂则无作用。选择性蛋白激酶C抑制剂Ro 31-7549增强了IL-1诱导的毛囊生长抑制,但本身不影响毛囊生长。这些发现表明,IL-1α对毛囊发挥快速的抗增殖作用,而毛发纤维生长抑制是一种继发反应。因此,IL-1可能通过对毛囊的直接生长抑制作用,在斑秃等炎症性脱发疾病的病理生理学中发挥作用。