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

M. T. Lotze, Y. L. Matory, S. E. Ettinghausen, A. A. Rayner, S. O. Sharrow, C. A. Seipp, M. C. Custer, S. A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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 105 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 105 U/kg to 15.4 x 105 U/kg. The limiting dose with this preparation was 3000 U/kg/hr by continuous administration or 106 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-γ 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.

Original languageEnglish (US)
Pages (from-to)2865-2875
Number of pages11
JournalJournal of Immunology
Volume135
Issue number4
StatePublished - 1985
Externally publishedYes

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Interleukin-2
Half-Life
Lymphocytes
Interleukin-11
Lymphokine-Activated Killer Cells
Neoplasms
Chills
Myalgia
Arthralgia
Interferons
Weight Gain
Blood Cells
Fever
Escherichia coli
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Lotze, M. T., Matory, Y. L., Ettinghausen, S. E., Rayner, A. A., Sharrow, S. O., Seipp, C. A., ... Rosenberg, S. A. (1985). 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. Journal of Immunology, 135(4), 2865-2875.

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. / Lotze, M. T.; Matory, Y. L.; Ettinghausen, S. E.; Rayner, A. A.; Sharrow, S. O.; Seipp, C. A.; Custer, M. C.; Rosenberg, S. A.

In: Journal of Immunology, Vol. 135, No. 4, 1985, p. 2865-2875.

Research output: Contribution to journalArticle

Lotze, MT, Matory, YL, Ettinghausen, SE, Rayner, AA, Sharrow, SO, Seipp, CA, Custer, MC & Rosenberg, SA 1985, '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', Journal of Immunology, vol. 135, no. 4, pp. 2865-2875.
Lotze, M. T. ; Matory, Y. L. ; Ettinghausen, S. E. ; Rayner, A. A. ; Sharrow, S. O. ; Seipp, C. A. ; Custer, M. C. ; Rosenberg, S. A. / 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. In: Journal of Immunology. 1985 ; Vol. 135, No. 4. pp. 2865-2875.
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AU - Ettinghausen, S. E.

AU - Rayner, A. A.

AU - Sharrow, S. O.

AU - Seipp, C. A.

AU - Custer, M. C.

AU - Rosenberg, S. A.

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N2 - 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 105 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 105 U/kg to 15.4 x 105 U/kg. The limiting dose with this preparation was 3000 U/kg/hr by continuous administration or 106 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-γ 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.

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