Differential effects of cyclosporin A and tacrolimus on the production of TGF-β: implications for the development of obliterative bronchiolitis after lung transplantation

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Abstract
The development of obliterative bronchiolitis is a common cause for failure of lung allografts. Fibrinogenesis can occur for a number of different reasons but some groups have suggested that cyclosporin A (CsA) and tacrolimus (FK506) have different effects on the cytokines which induce fibrinogenesis. We investigated the effect of tacrolimus and CsA in tissue culture and found that there was indeed a negative effect on human lung small airway epithelial cell proliferation by recombinant transforming growth factor‐β (TGF‐β), which was reversed by anti‐TGF‐β. The same effect was seen with CsA at immunosuppressive concentrations, which was also reversed by anti‐TGF‐β, whereas no such inhibition was seen with tacrolimus at immunosuppressive doses unless high concentrations were used. Free TGF‐β was confirmed as being elevated in the supernatant of cell culture wells with standard dose CsA as opposed to low dose CsA or tacrolimus using an ELISA assay.