Anti-allergic agent tranilast decreases development of obliterative airway disease in rat model of heterotopic tracheal transplantation.

Abstract

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.

CONCLUSION:

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.

• Authors: Yoshinori Okada, Yuji Matsumura, Kazuyoshi Shimada, Tetsu Sado, Takeshi Oyaizu, Takafumi Sugawara, Yasushi Matsuda, Yasushi Hoshikawa, Hiroto Takahashi, Masami Sato, Takashi Kondo
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 23 Issue 12 Pg. 1392-5 (Dec 2004) ISSN: 1053-2498 [Print] United States
• PMID: 15607669 (Publication Type: Journal Article)

Chemical References

• Anti-Allergic Agents
• ortho-Aminobenzoates
• tranilast

Topics

• Administration, Oral
• Animals
• Anti-Allergic Agents (administration & dosage)
• Bronchiolitis Obliterans (etiology, prevention & control)
• Graft Rejection (prevention & control)
• Major Histocompatibility Complex (immunology)
• Rats
• Rats, Inbred BN
• Rats, Inbred Lew
• Subcutaneous Tissue
• Trachea (pathology, transplantation)
• Transplantation, Heterotopic (adverse effects)
• ortho-Aminobenzoates (administration & dosage)