Synergy between cyclosporine and anti-IL-2 receptor monoclonal antibodies in rats. Functional studies of heart and kidney allografts.
Although cyclosporine has improved results of organ transplantation, treatment regimens using multiple agents are being evaluated both experimentally and clinically in attempts to diminish its often profound nephrotoxicity; some therapies act synergistically by differential inhibition of distinct steps of the rejection cascade. The effects on graft function of a full dose or a subclinical dose of CsA, ART-18, a monoclonal antibody (mAb) directed against the IL-2 receptor expressed on activated host cells, and a combination of low-dose CsA and ART-18, have been tested in rat recipients of both heart and kidney allografts. Renal graft function was assessed by several classic techniques; heart function by isolated perfusion methods. Full-dose CsA and combination treatment were most effective in both organ graft systems, with at least one-third of grafts surviving indefinitely. At seven days after transplantation, glomerular filtration rates and renal plasma flow of all grafted recipients were decreased as compared with normal; at 14 days, function in the best treatment groups had improved toward that of isografts. Similarly, cardiac output and stroke work index of best treatment groups were comparable to that of isografts. These functional studies complement previously reported immunological and immunohistological findings stressing that synergy occurs between subclinical doses of CsA and anti-IL-2-R mAb in two rat organ graft systems.
Ueda
H
H
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.
Cheung
Y C
YC
Masetti
P
P
Diaco
M
M
McCarter
M
M
Kupiec-Weglinski
J W
JW
Tilney
N L
NL
Martin
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003524:Cyclosporins / Q000627:therapeutic use*; D004357:Drug Synergism; D006085:Graft Survival; D006321:Heart / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D015375:Receptors, Interleukin-2