Jacobson M A, Hardy D, Connick E, Watson J, DeBruin M
Positive Health Program, Department of Medicine, University of California, San Francisco, CA 94110, USA.
J Infect Dis. 2000 Oct;182(4):1070-6. doi: 10.1086/315819. Epub 2000 Aug 28.
A phase 1 dose-escalation trial of a single subcutaneous dose of recombinant human (rh) interleukin (IL)-12 was conducted in medically stable human immunodeficiency virus (HIV)-infected patients with 100-500/microL absolute CD4(+) T lymphocytes. Subjects at each dose level were randomly assigned (3:1) to receive rhIL-12 or placebo. Among the 47 subjects enrolled, rhIL-12 was well tolerated at doses of 3-300 ng/kg, but 4 of 5 subjects who received rhIL-12 at 1000 ng/kg had severe adverse events. Dose-related increases in serum interferon-gamma occurred after rhIL-12 administration at doses > or =30 ng/kg. There was no effect of rhIL-12 on plasma HIV RNA or absolute CD4(+) T cell counts. However, dose-related increases in absolute CD8(+) T and NK cells were observed in subjects assigned to rhIL-12 doses of 30-300 ng/kg. Single rhIL-12 doses of 30-300 ng/kg were well tolerated and had biologic activity that could potentially be of benefit in the treatment of HIV disease or its complications.
对医学状况稳定、绝对 CD4(+) T 淋巴细胞计数为 100 - 500/微升的人类免疫缺陷病毒（HIV）感染患者进行了一项单剂量皮下注射重组人（rh）白细胞介素（IL）-12 的 1 期剂量递增试验。每个剂量水平的受试者被随机分配（3:1）接受 rhIL-12 或安慰剂。在入组的 47 名受试者中，rhIL-12 在 3 - 300 ng/kg 的剂量下耐受性良好，但 5 名接受 1000 ng/kg rhIL-12 的受试者中有 4 人出现严重不良事件。在剂量≥30 ng/kg 的 rhIL-12 给药后，血清干扰素-γ 出现剂量相关增加。rhIL-12 对血浆 HIV RNA 或绝对 CD4(+) T 细胞计数没有影响。然而，在分配接受 30 - 300 ng/kg rhIL-12 剂量的受试者中，观察到绝对 CD8(+) T 细胞和自然杀伤（NK）细胞的剂量相关增加。30 - 300 ng/kg 的单次 rhIL-12 剂量耐受性良好，并具有可能对治疗 HIV 疾病或其并发症有益的生物学活性。
