In vitro and in vivo effects of recombinant human interleukin-2 in naive miniature swine

Document Type

Journal Article

Publication Date

1-1-1992

Journal

Journal of Immunotherapy

Volume

11

Issue

3

DOI

10.1097/00002371-199204000-00003

Keywords

Interleukin-2; Lymphokine-activated killer cells-Miniature swine

Abstract

Recent data in mice have shown that early administration of recombinant human interleukin-2 (rIL-2) provides significant protection from lethal graft-versus-host disease. Because of the potential clinical importance of these findings, it wil be important to assess the effectiveness of this therapy in a large animal preclinical bone marrow transplantation model. We report here our initial studies of the in vitro and in vivo effects of rIL-2 in miniature swine. In vitro 4-day cultures of pig peripheral blood lymphocytes (PBL) in complete medium containing rIL-2 at 1,000 U/ml resulted in optimal proliferation and generation of lymphokine-activated killer (LAK) cells. A pig-mouse hybridoma cell line was found to be highly sensitive as a LAK cell target. Two naive pigs received 20,000 U/kg and 2 pigs received 100,000 U/kg of rIL-2 intravenously twice a day for 4 days. No clinical symptoms were seen during or after administration at the lower dose while both high dose-treated animals showed generalized erythema from days 2 to 4, and one showed mild diarrhea during this period. The disappearance of IL-2 activity from the serum showed two components: (1) an initial fast component with a half-time of ~60 min. LAK cell precursors disappeared form the peripheral circulation by 6 min after rIL-2 administration and began to recover by 6 h in the low dose recipients and only after 12 h in the high dose recipients. These data indicate that the effects of rIL-2 in vivo in miniature swine are very similar to those previously demonstrated in humans, and suggest that these animals should provide an excellent preclinical model for studies of the effects of rIL-2 on graft-versus-host disease. © 1992 Raven Press, Ltd., New York.

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