Exhaled nitric oxide correlates with experimental lung transplant rejection.
BACKGROUND
Increased nitric oxide production accompanies acute lung allograft rejection. Transforming growth factor-beta1 is an immunosuppressive cytokine capable of ameliorating acute rejection. The purpose of this study was to determine whether exhaled nitric oxide (eNO) concentrations correlated with the degree of acute rejection.


METHODS
A model of acute lung transplant rejection in the rat was developed, and concentrations of eNO were measured at the time of animal sacrifice. In group 1 (partial immunosuppression), donor lungs were pretreated with transforming growth factor-beta1 before implantation. In group 2 (fulminant acute rejection), no immunosuppression was used. In group 3 (full immunosuppression), recipients received cyclosporine. Group 4 were normal rats.


RESULTS
When measured from both lungs, eNO concentrations were 4.97+/-0.68 versus 6.73+/-2.90 ppb for groups 1 and 2, respectively (p = 0.58). When measured selectively from transplanted left lungs, eNO concentrations were 8.61+/-0.97 versus 42.14+/-7.27 ppb, respectively (p<0.001). In groups 3 and 4, eNO concentrations were 1.02+/-0.21 and 1.51+/-0.74 ppb, respectively.


CONCLUSIONS
Exhaled nitric oxide is elevated in fulminant acute rejection, is reduced after partial immunosuppression using transforming growth factor-beta1 gene therapy, and is in the normal range in cyclosporine-treated animals. The measurement of eNO correlates with the degree of acute lung allograft rejection and may serve as a noninvasive measure of acute lung transplant rejection in the clinical setting.
Mora
B N
BN
Department of Surgery, and Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Boasquevisque
C H
CH
Uy
G
G
McCarthy
T J
TJ
Welch
M J
MJ
Boglione
M
M
Patterson
G A
GA
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000032:analysis / Q000378:metabolism*; D015316:Genetic Therapy; D006084:Graft Rejection / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008168:Lung / Q000378:metabolism*; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019188:Organ Preservation Solutions / Q000627:therapeutic use; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D012119:Respiration; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D014184:Transplantation, Homologous
D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; D019188:Organ Preservation Solutions; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D016572:Cyclosporine