Anti-allergic agent tranilast decreases development of obliterative airway disease in rat model of heterotopic tracheal transplantation.
BACKGROUND
Tranilast is an anti-allergic agent known to inhibit the release of histamine, interleukin-1beta, transforming growth factor beta1, and platelet-derived growth factor from various cells and currently is used to treat allergic diseases, keloids, and hypertrophic scars. We evaluated the ability of tranilast to inhibit the development of obliterative airway disease (OAD) in a rat model of heterotopic tracheal transplantation.


METHODS
We transplanted tracheal segments from donor rats (Brown Norway) into subcutaneous pouches in major histocompatibility complex-incompatible recipient rats (Lewis). At Days 21 and 28 after transplantation, we histologically assessed the harvested allografts scored the degree of OAD, on a scale from zero to 4 as previously described, caused by fibroproliferative tissue.


RESULTS
Recipient animals treated orally with 400 mg/kg/day tranilast throughout the experiment showed significantly decreased OAD compared with control animals, with a histologic score of 1.1 +/- 0.4 vs 3.0 +/- 1.3, respectively (mean +/- SD, p=0.007), at Day 21 after transplantation and 2.0 +/- 1.4 vs 3.9 +/- 0.4, respectively (mean +/- SD, p=0.017), at Day 28 after transplantation.


CONCLUSIONS
These results showed that treatment with tranilast significantly decreased fibroproliferative airway changes associated with allograft rejection in a rat model of tracheal transplantation, suggesting that tranilast may be useful in preventing bronchiolitis obliterans after lung transplantation.
Okada
Yoshinori
Y
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. yokada@idac.tohoku.ac.jp
Matsumura
Yuji
Y
Shimada
Kazuyoshi
K
Sado
Tetsu
T
Oyaizu
Takeshi
T
Sugawara
Takafumi
T
Matsuda
Yasushi
Y
Hoshikawa
Yasushi
Y
Takahashi
Hiroto
H
Sato
Masami
M
Kondo
Takashi
T
D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage*; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000517:prevention & control*; D006084:Graft Rejection / Q000517:prevention & control; D008285:Major Histocompatibility Complex / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D040521:Subcutaneous Tissue; D014132:Trachea / Q000473:pathology / Q000637:transplantation*; D016042:Transplantation, Heterotopic / Q000009:adverse effects; D062367:ortho-Aminobenzoates / Q000008:administration & dosage*
D018926:Anti-Allergic Agents; D062367:ortho-Aminobenzoates; C012293:tranilast