Related Experiment Videos
Cyclosporine A inhibits lymphocyte migration into ovine peripheral nerve allografts
G M Hare1, S E Mackinnon, R Midha
1Department of Anaesthesia, Dalhousie University, Halifax, Nova Scotia, Canada.
Abstract:
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.
Insights
Cyclosporine A (CsA) effectively suppresses immune responses in nerve allografts. This study determined the optimal CsA dosage to prevent immune rejection in nerve transplantation, showing dose-dependent inhibition of lymphocyte migration.
Area of Science:
- Immunology
- Transplantation Science
- Pharmacology
Background:
- Nerve allograft rejection is a significant barrier to successful transplantation.
- Understanding immune cell infiltration is crucial for developing immunosuppressive strategies.
Purpose of the Study:
- To determine the effective dose of Cyclosporine A (CsA) for suppressing lymphocyte migration into nerve allografts.
- To establish a method for quantifying immune cell infiltration in nerve grafts.
Main Methods:
- Sheep received varying daily doses of subcutaneous CsA (0-15 mg/kg/day) for two weeks prior to nerve allograft implantation.
- Autologous 111indium-labeled lymphocytes were administered intravenously to assess migration into grafts after seven days.
- Gamma radioactivity in nerve tissue quantified lymphocyte infiltration, with blood CsA levels measured by radioimmunoassay.
Main Results:
- Lymphocyte migration into nerve allografts was significantly higher than into autografts in control animals.
- CsA administration demonstrated a dose-dependent inhibition of lymphocyte migration into nerve allografts.
- Effective blood CsA levels correlated with reduced immune cell infiltration, indicating successful immunosuppression.
Conclusions:
- Daily CsA administration effectively suppresses lymphocyte migration into nerve allografts.
- This study provides a basis for CsA dosing strategies in nerve transplantation to prevent rejection.
- Quantifying lymphocyte migration is a reliable method for assessing immunosuppressive efficacy in nerve allografts.