Systemic administration of recombinant human interleukin-2 in mice. 1984

A E Chang, and C L Hyatt, and S A Rosenberg

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 greater than or equal to 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 greater than or equal to 8 units/ml for greater than 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.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D007694 Killer Cells, Natural Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type. NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D008222 Lymphokines Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. Lymphocyte Mediators,Mediators, Lymphocyte
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D003602 Cytotoxicity, Immunologic The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement. Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities

Related Publications

A E Chang, and C L Hyatt, and S A Rosenberg
February 1989, Journal of biological response modifiers,
A E Chang, and C L Hyatt, and S A Rosenberg
May 1989, Blood,
A E Chang, and C L Hyatt, and S A Rosenberg
June 1987, The Journal of clinical investigation,
A E Chang, and C L Hyatt, and S A Rosenberg
January 1987, Drug metabolism and disposition: the biological fate of chemicals,
A E Chang, and C L Hyatt, and S A Rosenberg
June 1992, Lymphokine and cytokine research,
A E Chang, and C L Hyatt, and S A Rosenberg
August 1985, Journal of immunology (Baltimore, Md. : 1950),
A E Chang, and C L Hyatt, and S A Rosenberg
September 1986, Journal of immunology (Baltimore, Md. : 1950),
A E Chang, and C L Hyatt, and S A Rosenberg
October 1984, Journal of biological response modifiers,
Copied contents to your clipboard!