In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2.
Purified recombinant human interleukin 2 (RIL 2) derived from E. coli containing the inserted gene encoding for IL 2 was administered to 20 patients with a variety of malignancies. Toxicity was dose related and included fever, chills, malaise, arthralgias, myalgias, and unexpectedly, weight gain related to marked fluid retention. All patients receiving more than 10(5) U/kg total cumulative dose developed evidence of fluid retention, and all patients requiring discontinuance of RIL 2 (11/20) received total doses of between 2.54 X 10(5) U/kg to 15.4 X 10(5) U/kg. The limiting dose with this preparation was 3000 U/kg/hr by continuous administration or 10(6) U/kg by bolus administration. IL 2 was rapidly cleared from the plasma, with a half life of 6.9 min, and a later delayed clearance was consistent with a two-compartment model, with slower release from the extravascular space back into the plasma compartment. A marked change in lymphoid cells in the periphery was noted with an early depletion of all lymphoid cells, followed by an expansion of such cells with continuous IL 2 administration. A twofold to 16-fold expansion of total lymphoid cells in the peripheral blood could be demonstrated. TAC+ cells representing up to 25% of the circulating peripheral blood mononuclear cells could be demonstrated with 3 wk of continuous RIL 2 administration. Interferon-gamma levels increased in patients treated with IL 2. Precursors of lymphokine-activated killer cells generated under standard conditions were depleted within 2 to 3 min after IL 2 administration, but repopulated the peripheral blood after 7 to 10 days of continuous IL 2 administration. No tumor regression was seen in any of the cancer patients treated with IL 2 alone.
Lotze
M T
MT
Matory
Y L
YL
Ettinghausen
S E
SE
Rayner
A A
AA
Sharrow
S O
SO
Seipp
C A
CA
Custer
M C
MC
Rosenberg
S A
SA
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D005260:Female; D006207:Half-Life; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007263:Infusions, Parenteral; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone