Effect of Inhaled Tacrolimus on Cellular and Humoral Rejection to Prevent Posttransplant Obliterative Airway Disease

This study aimed to investigate the pharmacokinetics after tacrolimus aerosol inhalation and to assess its efficacy to suppress acute and chronic airway allograft rejection. Orthotopic tracheal transplantations were performed and tacrolimus (4 mg/kg) was administered orally (PO) or via aerosol (AER)...

Full description

Saved in:
Bibliographic Details
Published in:American journal of transplantation 2007-07, Vol.7 (7), p.1733-1742
Main Authors: Schrepfer, S., Deuse, T., Reichenspurner, H., Hoffmann, J., Haddad, M., Fink, J., Fischbein, M. P., Robbins, R. C., Pelletier, M. P.
Format: Article
Language:English
Subjects:
Administration, Inhalation
Aerosol
Airway Obstruction - prevention & control
Animals
Antibody Formation - drug effects
Biological and medical sciences
cellular rejection
Chronic obstructive pulmonary disease, asthma
Cytokines - analysis
Graft Rejection - immunology
Graft Rejection - prevention & control
humoral rejection
Immunity, Cellular - drug effects
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - pharmacokinetics
Immunosuppressive Agents - therapeutic use
inhaled immunosuppression
Male
Medical sciences
OAD development
Pneumology
Postoperative Complications - prevention & control
Prevention and actions
Public health. Hygiene
Public health. Hygiene-occupational medicine
Rats
Rats, Inbred BN
Rats, Inbred Lew
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
tacrolimus
Tacrolimus - administration & dosage
Tacrolimus - pharmacokinetics
Tacrolimus - therapeutic use
Trachea - transplantation
Transplantation, Homologous - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study aimed to investigate the pharmacokinetics after tacrolimus aerosol inhalation and to assess its efficacy to suppress acute and chronic airway allograft rejection. Orthotopic tracheal transplantations were performed and tacrolimus (4 mg/kg) was administered orally (PO) or via aerosol (AER). Tracheal tissue level AUCs0–12 were similar in both treatment groups, but blood AUCs0–12 were approximately 5.5‐fold lower with AER (p < 0.001). Interestingly, only PO animals showed elevated BUN, cholesterol and triglycerides on POD 60 (p < 0.05). Histology of grafts harvested after 6 and 60 days revealed that both treatment groups were similarly effective in suppressing graft mononuclear infiltration (p < 0.001). Cellular immune activation (assessed by IFN‐γ‐ and IL‐4‐ELISPOTS), however, was far more effectively suppressed by tacrolimus PO (p < 0.001). In both treatment groups, the vigorous alloreactive IgM‐antibody surge was effectively inhibited (p < 0.001). Due to the insufficient systemic cellular immunosuppression, discontinuation of tacrolimus AER resulted in a far stronger (3.5‐fold) graft infiltration on POD 8 compared to PO (p < 0.001). Tacrolimus aerosol reduces systemic side effects and effectively protects the airway graft from early cellular rejection and chronic obliterative airway disease. Tacrolimus aerosol inhalation effectively prevents orthotopic rat tracheal allografts from acute and chronic rejection without intense systemic immunosuppression.
ISSN:1600-6135
1600-6143
DOI:10.1111/j.1600-6143.2007.01858.x