OBJECTIVE: Profound immunosuppression and extensive fibrotic changes in the skin are characteristic for graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Transforming growth factor (TGF)-beta is a potent immunosuppressive cytokine that plays an important regulatory role in the immune response. In addition, TGF-beta promotes wound repair but has also been implicated in tissue fibrosis. These characteristics prompted us to question whether serum TGF-beta levels would be associated with GVHD after BMT. METHODS: In this study, total TGF-beta1 levels in serum from HLA-identical BMT recipients before and at several time intervals after transplantation were quantified and correlated with platelet and white blood cell (WBC) counts and with the presence of acute and chronic GVHD in a multivariate analysis. RESULTS: TGF-beta1 levels were readily detectable in healthy controls and in BMT recipients before BMT. In all patients, a rapid drop in TGF-beta1 levels was seen during the BMT conditioning regimen. After 20-50 days postBMT, TGF-beta1 levels started to increase to normal levels. Platelet and WBC counts were strongly correlated with TGF-beta1 levels (r=0.810, P<0.001, and r=0.733, P<0.001, respectively). Multivariate analysis also revealed that TGF-beta1 levels were significantly increased during chronic GVHD and that the increase during acute GVHD reached levels of significance (P=0.009 and P=0.053, respectively). CONCLUSIONS: These results show that total TGF-beta1 levels correlate significantly with platelet and WBC counts and that chronic GVHD is associated with an increase in serum TGF-beta1, independent of platelet or WBC counts.
OBJECTIVE: Profound immunosuppression and extensive fibrotic changes in the skin are characteristic for graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Transforming growth factor (TGF)-beta is a potent immunosuppressive cytokine that plays an important regulatory role in the immune response. In addition, TGF-beta promotes wound repair but has also been implicated in tissue fibrosis. These characteristics prompted us to question whether serum TGF-beta levels would be associated with GVHD after BMT. METHODS: In this study, total TGF-beta1 levels in serum from HLA-identical BMT recipients before and at several time intervals after transplantation were quantified and correlated with platelet and white blood cell (WBC) counts and with the presence of acute and chronic GVHD in a multivariate analysis. RESULTS:TGF-beta1 levels were readily detectable in healthy controls and in BMT recipients before BMT. In all patients, a rapid drop in TGF-beta1 levels was seen during the BMT conditioning regimen. After 20-50 days postBMT, TGF-beta1 levels started to increase to normal levels. Platelet and WBC counts were strongly correlated with TGF-beta1 levels (r=0.810, P<0.001, and r=0.733, P<0.001, respectively). Multivariate analysis also revealed that TGF-beta1 levels were significantly increased during chronic GVHD and that the increase during acute GVHD reached levels of significance (P=0.009 and P=0.053, respectively). CONCLUSIONS: These results show that total TGF-beta1 levels correlate significantly with platelet and WBC counts and that chronic GVHD is associated with an increase in serum TGF-beta1, independent of platelet or WBC counts.