SYSTEMIC ADMINISTRATION OF RECOMBINANT HUMAN INTERLEUKIN-2 IN MICE

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 3  (5) , 561-572
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. A variety of routes of administration of RIL-2 in mice were studied to maximize the bioavailability of this lymphokine. The serum half-life after i.v. administration was 1.6 .+-. 0.3 min (mean .+-. SEM [standare error of the mean], n = 3). The i.v. and s.c. administration resulted in RIL-2 serum levels .gtoreq. 10 u/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 i.p. or s.c., and resulted in RIL-2 serum levels .gtoreq. 8 .mu./ml for > 4 days. RIL-2 given i.p. 3 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 allogenic P815 was found in mice receiving RIL-2 i.p. 3 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 3 different cell-mediated cytotoxic mechanisms and has potential applications in the treatment of tumors and immunodeficient conditions.