Use of mixed lymphocyte reaction to identify subimmunosuppressive FK-506 levels in mice
✍ Scribed by Ramsay A. Ellis; Michael J. Brenner; Susan E. Mackinnon; Terence M. Myckatyn; Daniel A. Hunter
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 273 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0738-1085
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
The immunosuppressive agent FK‐506 has a well‐described neuroregenerative effect that is mediated by a mechanism independent of calcineurin inhibition. FK‐506 levels that fall below the threshold for immunosuppression could therefore potentially enhance nerve regeneration while minimizing toxicity. The purpose of this study was to characterize the dose‐dependent effects of FK506 on T‐cell proliferation, and establish a subimmunosuppressive dosing regimen for FK‐506 in mice. Forty BALB/cJ mice were randomized to four groups corresponding to 0, 0.25, 0.5, or 1.0 mg/kg/day doses of FK‐506. Ten days postoperatively, animals were sacrificed, and mixed lymphocyte reaction assays were performed to quantify the immune response to nerve allografts. Mice receiving 0.25 and 0.5 mg/kg/day of FK‐506 exhibited a robust T‐cell proliferation response, with stimulation indices approaching those of untreated animals. Mice treated with 1.0 mg/kg/day of FK‐506 demonstrated significantly decreased T‐cell proliferation. These results establish 0.5 mg/kg/day as an upper limit for subimmunosuppressive FK‐506 administration. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:276–282 2003