PT  - JOURNAL ARTICLE
AU  - Katrin Hostettler
AU  - Jörg Halter
AU  - Didier Lardinois
AU  - Michael Roth
AU  - Michael Tamm
TI  - Dose-dependent pro- or anti-proliferative effects of calcineurin inhibitors in bronchiolitis obliterans following allogeneic stem cell transplantation
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p2001
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p2001.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p2001.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Background: Bronchiolitis obliterans (BO) is a common complication after allogeneic stem cell transplantation (SCT), characterized by fibroproliferation, fibrotic occlusion of small airways, and poor prognosis. As BO is strongly associated with chronic graft-versus-host disease (GVHD), it is believed to be a pulmonary manifestation of chronic GVHD. The management of BO comprises the augmentation of immunosuppressive therapy, but treatment response is generally poor. Here, we investigated the effect of methylprednisolone (mPRED), cyclosporine A (CsA), and tacrolimus (FK506) on the proliferative capacity of fibroblasts isolated from surgical lung biopsies of SCT patients with histologically proven BO.Methods: Primary cultures of human lung fibroblasts were grown from surgical lung biopsies obtained from 8 patients with BO after SCT. Fibroblasts were stimulated with increasing concentrations of each drug, and cell proliferation was assessed by [3H]-thymidine incorporation.Results: In fibroblasts derived from patients with BO after SCT low concentrations of CsA (0.01 mg/l, 0.1 mg/l) and FK506 (0.001 mg/l, 0.01 mg/l) significantly induced proliferation compared to untreated cells. Only high dose CsA (50 mg/l) and FK506 (5 mg/l) exerted an anti-proliferative effect in primary human lung fibroblasts derived from BO patients. mPRED caused an inhibition of proliferation in clinically relevant concentrations (10 mg/l, 50 mg/l).Conclusion: Our data suggest that calcineurin inhibitors such as CsA and FK506 have no beneficial effect during the fibroproliferative phase of BO following allogeneic SCT.