Kintzel P E, Calis K A
Audie L. Murphy Memorial Veterans Hospital, San Antonio, TX.
Clin Pharm. 1991 Feb;10(2):110-28.
The chemical properties, pharmacology, immunology, pharmacokinetics, clinical trials, adverse effects, and dosage and administration of recombinant interleukin-2 are reviewed. Recombinant interleukin-2 is an immunomodulating agent that stimulates the proliferation, activation, and differentiation of T and B cells, natural killer cells, and thymocytes. Two recombinant interleukin-2 products, aldesleukin and teceleukin, have been extensively studied. Most clinical experience with recombinant interleukin-2 has involved the treatment of renal cell carcinoma, melanoma, and colorectal cancer with a National Cancer Institute protocol. Patients with renal cell cancer and melanoma, who historically respond poorly to conventional therapy, have responded to therapy with recombinant interleukin-2. Recombinant interleukin-2 has been administered alone and in combination with lymphokine-activated killer cells, tumor-infiltrating lymphocytes, and interferons alfa and beta. In addition, the effect of dosage, administration rate, dosage schedule, route of administration, and cyclophosphamide pretreatment have been investigated. The adverse effects of recombinant interleukin-2 are generally reversible but are frequently severe and dose-related. Dose-limiting adverse effects include hypotension, edema, and renal dysfunction. Since hemodynamic monitoring and supportive care are essential, recombinant interleukin-2 should be administered in a critical-care setting by trained personnel. Recombinant interleukin-2 represents an advance in the therapy of renal cell cancer and melanoma and offers a new approach to the treatment of other refractory or recurrent malignancies.
本文综述了重组白细胞介素-2的化学性质、药理学、免疫学、药代动力学、临床试验、不良反应以及剂量与用法。重组白细胞介素-2是一种免疫调节剂，可刺激T细胞、B细胞、自然杀伤细胞和胸腺细胞的增殖、活化和分化。两种重组白细胞介素-2产品，即阿地白介素和替西白介素，已得到广泛研究。重组白细胞介素-2的大多数临床经验来自于按照美国国立癌症研究所方案治疗肾细胞癌、黑色素瘤和结直肠癌。肾细胞癌和黑色素瘤患者以往对传统疗法反应不佳，但对重组白细胞介素-2治疗有反应。重组白细胞介素-2已单独使用，并与淋巴因子激活的杀伤细胞、肿瘤浸润淋巴细胞以及α和β干扰素联合使用。此外，还研究了剂量、给药速率、给药方案、给药途径以及环磷酰胺预处理的效果。重组白细胞介素-2的不良反应一般是可逆的，但通常较为严重且与剂量相关。剂量限制性不良反应包括低血压、水肿和肾功能不全。由于血流动力学监测和支持治疗至关重要，重组白细胞介素-2应由经过培训的人员在重症监护环境中给药。重组白细胞介素-2代表了肾细胞癌和黑色素瘤治疗的进展，并为其他难治性或复发性恶性肿瘤的治疗提供了一种新方法。
