Systemic administration of recombinant human interleukin-2 in mice

Alfred E. Chang, Cornelia L. Hyatt, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

The production of recombinant human interleukin-2 (RIL-2) in large amounts has made possible studies of the in vivo effects of this lymphokine in the normal murine host. We have studied a variety of routes of administration of RIL-2 in mice to maximize the bioavailability of this lymphokine. The serum half-life after intravenous administration was 1.6 ± 0.3 min (mean ± SEM, n + 3). Intraperitoneal and subcutaneous administration resulted in RIL-2 serum levels ≥ 10 units/ml for 3-5 h, and was prolonged by gelatin for 7-11 h. Continuous infusion of RIL-2 was accomplished with osmotic pumps placed intraperitoneally or subcutaneously, and resulted in RIL-2 serum levels ≥ 8 units/ml for > 4 days. RIL-2 given intraperitoneally three times daily for 3 days enhanced natural killer activity of splenocytes as measured by lysis of YAC cells. Specific augmentation of C57BL/6 splenocyte cytotoxicity to a secondary challenge of irradiated allogeneic P815 was found in mice receiving RIL-2 intraperitoneally three times daily for 3 days. The continuous administration of RIL-2 over a 4-day period resulted in the in vivo generation of lymphokine-activated killer cells in the spleen and peritoneal exudate. The exogenous administration of RIL-2 in the normal murine host enhances three different cell-mediated cytotoxic mechanisms and has potential applications in the treatment of tumors and immunodeficient conditions.

Original languageEnglish (US)
Pages (from-to)561-572
Number of pages12
JournalJournal of Biological Response Modifiers
Volume3
Issue number5
StatePublished - Oct 1984

Keywords

  • Lymphokine-activated killer cells
  • Natural killer cells
  • Osmotic pump
  • Recombinant IL-2

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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