Long-term laryngeal allograft survival using low-dose everolimus.
OBJECTIVE
The purpose of this study was to explore the mechanism and utility of everolimus as a single-agent therapy in preventing mouse laryngeal allograft rejection.


METHODS
Prospective animal study.


METHODS
Academic research at a tertiary medical center.


METHODS
Fifteen recipient mice (five per group) were injected with everolimus (1 mg/kg/d) until euthanized at 15, 30, and 60 days posttransplantation. Five mice received transplants without immunosuppression and were euthanized at day 15. Larynges were graded for rejection severity. Draining lymph nodes and spleens were evaluated by flow cytometry to assess the systemic immunological environment.


RESULTS
Each time group demonstrated minor allograft rejection (rejection severity scores: 2.51, 2.46, 2.78; no rejection, 1; severe, 6). This was not significantly different between groups. Everolimus-treated mice had significantly less rejection at all time points compared with non-immunosuppressed mice. Flow cytometry showed a blunted cytotoxic T-cell response, differentiation favoring regulatory T-cells, and decreased number and function of dendritic cells.


CONCLUSIONS
Everolimus successfully prevents laryngeal allograft rejection up to 60 days posttransplantation. It appears to increase the production of regulatory T-cells while decreasing cytotoxic T-cell and dendritic cell response. Everolimus alone or in combination with other immunosuppressants may enable laryngeal transplantation to become a viable reconstructive option following laryngectomy for malignancy.
Lott
David G
DG
Cleveland Clinic Head and Neck Institute, Cleveland, OH, USA.
Dan
Olivia
O
Lu
Lina
L
Strome
Marshall
M
D000818:Animals; D000068338:Everolimus; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007830:Larynx / Q000637:transplantation*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus