Long-term laryngeal allograft survival using low-dose everolimus

David G Lott, Olivia Dan, Lina Lu, Marshall Strome

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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. Study Design: Prospective animal study. Setting: Academic research at a tertiary medical center. Subjects and 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.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalOtolaryngology - Head and Neck Surgery
Volume142
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

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Allografts
Regulatory T-Lymphocytes
Dendritic Cells
Flow Cytometry
T-Lymphocytes
Laryngectomy
Immunosuppressive Agents
Larynx
Immunosuppression
Cell Differentiation
Spleen
Cell Count
Transplantation
Lymph Nodes
Everolimus
Prospective Studies
Transplants
Research
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Surgery

Cite this

Long-term laryngeal allograft survival using low-dose everolimus. / Lott, David G; Dan, Olivia; Lu, Lina; Strome, Marshall.

In: Otolaryngology - Head and Neck Surgery, Vol. 142, No. 1, 01.2010, p. 72-78.

Research output: Contribution to journalArticle

Lott, David G ; Dan, Olivia ; Lu, Lina ; Strome, Marshall. / Long-term laryngeal allograft survival using low-dose everolimus. In: Otolaryngology - Head and Neck Surgery. 2010 ; Vol. 142, No. 1. pp. 72-78.
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