In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of the Jurkat cell line-derived interleukin 2.
A total of 12 patients with cancer or the acquired immunodeficiency syndrome have been treated with Jurkat-derived purified human interleukin 2 (IL 2). The toxicity was dose-related and consisted primarily of fever, chills, malaise, and mild reversible hepatic dysfunction. No evidence of clinical efficacy was seen when IL 2 was administered at doses of up to 2000 micrograms by bolus or continuous infusion once a week for 4 wk. No significant chronic immunologic effects (changes in mitogen responsiveness of induction of cytotoxic cells) were demonstrated. IL 2 was measured in the serum of patients, and a half-life of approximately 5 to 7 min was demonstrated with a second component of clearance of 30 to 120 min. Heating the serum at 56 degrees C for 30 min allowed for detection of smaller quantities of IL 2 by removing a serum inhibitor whose effect was seen at dilutions of up to 1/80 in our biologic assay. Sustained levels of IL 2 could be maintained by continuous infusion. Acute effects of IL 2 administration included a rapid decrease in peripheral mononuclear cells with a shift to cells of macrophage lineage and a rapid decrease in total T lymphocytes and T lymphocyte subsets. IL 2 responsiveness of peripheral mononuclear cells decreased within 15 min of IL 2 administration, with a concurrent decrease in the ability to generate lymphokine-activated killer cells. These changes did not recover until 48 hr after IL 2 administration. A rise in serum ACTH and cortisol levels was seen after the administration of 1 to 2 mg of IL 2. Future studies will evaluate the role of larger quantities of recombinant IL 2 given alone or in conjunction with in vitro-generated lymphokine-activated killer cells.
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D000368:Aged; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D008175:Lung Neoplasms / Q000628:therapy; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000628:therapy; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D012509:Sarcoma / Q000628:therapy; D012514:Sarcoma, Kaposi / Q000628:therapy; D012878:Skin Neoplasms / Q000628:therapy
D007376:Interleukin-2