Pirfenidone: A novel anti-fibrotic agent and progressive chronic allograft rejection.
In our established model of heterotopic tracheal transplantation, at day 28 following transplantation, obliteration of the lumen is observed, which is histologically similar to that seen in Obliterative Bronchiolitis (OB). Pirfenidone (Pir) is a novel anti-fibrotic agent that causes no immunosuppression, but does downregulate the production of TGF-beta and collagen in vitro. We hypothesized that when used in this in vivo model, that Pir may alter the observed luminal fibrosis and obliteration.


METHODS
The treatment groups were: CSA, Pir and CSA, Pir only (n=6 each). Luminal supernatants and tissue were obtained from these groups at day 28. H&E staining was completed, as well as MTS proliferation assays, and TGF-beta ELISA on the fluids.


RESULTS
The CSA-Pir combined treatment group was the least fibrogenic in vitro (p<0.001). The TGF-beta levels were elevated in all groups (range 203-372 pg/ml). The H&E staining revealed that the luminal obliteration was less organized in the combined CSA-Pir group.


CONCLUSIONS
Our study shows that the combination of CSA-Pir results in a less fibrogenic luminal fluid and a less dense fibrous luminal plug. Pir should be further studied in obliterative airways disease (OAD).
Dosanjh
A
A
Stanford University, Stanford, CA, USA.
Ikonen
T
T
Wan
B
B
Morris
R E
RE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005355:Fibrosis / Q000517:prevention & control*; D006084:Graft Rejection / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling; D014132:Trachea / Q000187:drug effects* / Q000637:transplantation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007166:Immunosuppressive Agents; D011728:Pyridones; D016572:Cyclosporine; C093844:pirfenidone