Hughes J R, Hughes V F, Trull A K, Metcalfe S M
University of Bath, School of Biology and Biochemistry, UK.
Transplantation. 1999 Aug 27;68(4):583-6. doi: 10.1097/00007890-199908270-00025.
Transforming growth factor beta-1 (TGFbeta1) is pro-fibrotic in addition to being a potent immunosuppressive cytokine. Cyclosporine (cyclosporin A[CsA]) has been found to increase circulating TGFbeta1 levels in patients (1, 2). To determine whether tacrolimus (FK506) similarly increases TGFbeta1 we have measured TGFbeta levels in blood samples from liver graft recipients who were of known TGFbeta1-responder status.
Sequential serum and plasma samples were obtained from liver transplant recipients in the UK trial of tacrolimus versus microemulsified CsA, with a follow up period of between 50 and 265 days. Twelve patients received CsA and 13 received tacrolimus. Active and total TGFbeta1 protein were measured and plasma beta thromboglobulin (betaTG) levels were used as an indirect indication of platelet-derived TGFbeta contamination of samples.
We found no correlation between trough drug levels and active TGFbeta1 levels in serum of either set of patients. Plasma beta thromboglobulin was detected in platelet-depleted plasma samples, indicative of platelet damage before plasma separation.
Neither CsA nor tacrolimus induced active TGFbeta1 blood levels in liver transplant recipients during a follow up period of < or = 265 days.
转化生长因子β-1(TGFβ1)除了是一种强效免疫抑制细胞因子外,还具有促纤维化作用。已发现环孢素(环孢菌素A[CsA])可使患者循环中的TGFβ1水平升高(1,2)。为了确定他克莫司(FK506)是否同样会使TGFβ1升高,我们检测了已知TGFβ1反应状态的肝移植受者血样中的TGFβ水平。
在英国进行的他克莫司与微乳化CsA对比试验中,从肝移植受者获取序贯血清和血浆样本,随访期为50至265天。12例患者接受CsA,13例接受他克莫司。检测活性和总TGFβ1蛋白,并将血浆β-血小板球蛋白(βTG)水平作为样本中血小板衍生的TGFβ污染的间接指标。
我们发现两组患者血清中的谷值药物水平与活性TGFβ1水平之间均无相关性。在血小板缺乏的血浆样本中检测到血浆β-血小板球蛋白,表明在血浆分离前存在血小板损伤。
在≤265天的随访期内,CsA和他克莫司均未诱导肝移植受者血液中活性TGFβ1水平升高。