TY - JOUR
T1 - Thalidomide as replacement for steroids in immunosuppression after lung transplantation
AU - Uthoff, Kay
AU - Zehr, Kenton J.
AU - Gaudin, Paul B.
AU - Kumar, Pankaj
AU - Cho, Peter W.
AU - Vogelsang, Georgia
AU - Hruban, Ralph H.
AU - Baumgartner, William A.
AU - Stuart, R. Scott
PY - 1995/2
Y1 - 1995/2
N2 - Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (α-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. It was not efficacious in combination with low-dose cyclosporin A. This drug may have a significant impact after clinical lung transplantation by reducing steroid-associated complications.
AB - Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (α-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. It was not efficacious in combination with low-dose cyclosporin A. This drug may have a significant impact after clinical lung transplantation by reducing steroid-associated complications.
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U2 - 10.1016/0003-4975(94)00870-D
DO - 10.1016/0003-4975(94)00870-D
M3 - Article
C2 - 7847937
AN - SCOPUS:0028891051
VL - 59
SP - 277
EP - 282
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
SN - 0003-4975
IS - 2
ER -