Schnittman S M, Vogel S, Baseler M, Lane H C, Davey R T
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
J Infect Dis. 1994 May;169(5):981-9. doi: 10.1093/infdis/169.5.981.
Interferon-alpha (IFN-alpha) can inhibit human immunodeficiency virus (HIV-1) replication and is effective in treating Kaposi's sarcoma; interleukin-2 (IL-2) can increase circulating lymphocytes in HIV-1-infected patients. The safety of combination treatment with recombinant (r)IFN-alpha 2b and IL-2 was evaluated in HIV-1-infected patients with > 200 CD4+ T cells/mm3. A maximal tolerated dose of rIFN-alpha 2b was determined for 17 patients; then they received in combination 3, 6, or 12 x 10(6) IU/day rIL-2, given intravenously over 21 days. Twelve patients ultimately received the combination, 9 for the full 21 days. Significant toxicities included flu-like symptoms, anemia, transaminemia, and depression. Transient increases in CD4+ T cell percentages and spontaneous lymphocyte blast transformation were observed. Quantitative microcultures demonstrate a decline in HIV titers in patients receiving rIFN-alpha 2b (5/9) with a further decline on addition of rIL-2 (7/9). In summary, continuous rIL-2 at 6 x 10(6) IU/day in combination with rIFN-alpha 2b was reasonably tolerated and provided preliminary evidence of immunomodulatory and antiviral activity.
α干扰素（IFN-α）可抑制人类免疫缺陷病毒（HIV-1）复制，对治疗卡波西肉瘤有效；白细胞介素-2（IL-2）可增加HIV-1感染患者的循环淋巴细胞数量。对CD4+T细胞>200/mm3的HIV-1感染患者评估了重组（r）IFN-α 2b与IL-2联合治疗的安全性。为17例患者确定了rIFN-α 2b的最大耐受剂量；然后他们接受了3、6或12×10⁶IU/天的rIL-2联合治疗，静脉注射21天。最终12例患者接受了联合治疗，9例完成了整个21天的治疗。显著的毒性反应包括流感样症状、贫血、转氨酶升高和抑郁。观察到CD4+T细胞百分比短暂升高以及自发淋巴细胞转化。定量微量培养显示，接受rIFN-α 2b治疗的患者（5/9）HIV滴度下降，加用rIL-2后进一步下降（7/9）。总之，每天6×10⁶IU的持续rIL-2与rIFN-α 2b联合使用耐受性尚可，并提供了免疫调节和抗病毒活性的初步证据。
