Cyclosporine A inhibits lymphocyte migration into ovine peripheral nerve allografts.
Lymphocyte migration into nerve allografts was measured to estimate the cyclosporine A (CsA) dose required to suppress rejection. Twelve outbred sheep received daily subcutaneous CsA at 0, 5, 10, or 15 mg/kg/day for 2 weeks prior to implantation of multiple heterotopic subcutaneous nerve grafts. Lymphocyte migration was determined after 7 days by an intravenous pulse of autologous 111indium-labeled lymphocytes and subsequent quantitation of gamma radioactivity in nerve tissue (CPM/g, mean +/- SEM). Measurement by radioimmunoassay revealed a dose-dependent increase in blood cyclosporine levels. Lymphocyte migration into autografts (404+/-44) was significantly less than migration into allografts (16,554+/-2,049), in control animals (P < 0.01). A dose-dependent inhibition of lymphocyte migration into nerve allografts was observed with counts of 7,662+/-1,692, 4,083+/-1,112, and 1,561+/-232 in sheep receiving 5, 10, or 15 mg/kg/day of CsA, respectively. Daily CsA administration produced effective blood levels and immunosuppression sufficient to inhibit lymphocyte migration into nerve allografts.
Hare
G M
GM
Department of Anaesthesia, Dalhousie University, Halifax, Nova Scotia, Canada.
Mackinnon
S E
SE
Midha
R
R
Wong
P Y
PY
Au
B
B
Munro
C
C
Andrade
W
W
Hunter
D A
DA
Hay
J B
JB
D000818:Animals; D002464:Cell Migration Inhibition; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D018655:Lymphocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D010525:Peripheral Nerves / Q000276:immunology / Q000637:transplantation*; D012756:Sheep; D014182:Transplantation, Autologous; D016042:Transplantation, Heterotopic / Q000276:immunology; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine