In vitro and in vivo effects of recombinant human interleukin-2 in naive miniature swine.
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 will 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 approximately 10 min and (2) a slow component with a half-time of approximately 60 min. LAK cell precursors disappeared from 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakajima
K
K
Transplantation Biology Research Center, Massachusetts General Hospital, Charlestown 02129.
Smith
C V
CV
Mixon
A
A
Sykes
M
M
Guzzetta
P C
PC
Spitzer
T R
TR
Eckhaus
M A
MA
Sachs
D H
DH
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects
D015703:Antigens, CD; D007376:Interleukin-2; D011994:Recombinant Proteins