Thalidomide as replacement for steroids in immunosuppression after lung transplantation.
Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (alpha-phthalimidoglutarimide), a sedative drug with known immunomodulatory properties, was used to replace corticosteroids after canine lung transplantation. Fifteen mongrel dogs underwent single-lung transplantation: group I (n = 5) received cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Group II (n = 5) received standard immunosuppression of cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and prednisone (2 mg/kg once a day), and group III (n = 5) received cyclosporin A (10 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Open lung biopsy and bronchoscopy were performed weekly until sacrifice on day 28. Serum thalidomide and cyclosporin A levels were followed up weekly. Group I showed essentially no rejection until week 2 and minimal rejection (grade 1) until day 28. Group II had moderate rejection (grade 2) of the graft at all time points. Group III animals had moderate to severe rejection (grades 3 to 4) after 21 days (p < 0.05 for group I versus groups II and III). The number of clinically evident episodes of pneumonia was also significantly lower in group I than in groups II and III (p < 0.05). We conclude that thalidomide appears to replace corticosteroids effectively in early postoperative immunosuppression after lung transplantation and is associated with a decreased incidence of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)
Uthoff
K
K
Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Zehr
K J
KJ
Gaudin
P B
PB
Kumar
P
P
Cho
P W
PW
Vogelsang
G
G
Hruban
R H
RH
Baumgartner
W A
WA
Stuart
R S
RS
D000818:Animals; D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004285:Dogs; D006084:Graft Rejection; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation; D011014:Pneumonia / Q000209:etiology; D011183:Postoperative Complications; D011241:Prednisone / Q000627:therapeutic use; D013792:Thalidomide / Q000627:therapeutic use*; D014945:Wound Healing
D007166:Immunosuppressive Agents; D013792:Thalidomide; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone