Markers of cell activation and apoptosis in bone marrow mononuclear cells of patients with autoimmune hepatitis type 1 and primary biliary cirrhosis

Background/Aims: We have reported quantitative and qualitative differences in bone marrow (BM) progenitor cells in autoimmune hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC). This study investigated the apoptotic features and cytokine suppressors of haematopoiesis in long-term cultures of BM mononuclear cells (BMMCs) from AIII-I and PBC patients. Methods: Apoptotic markers and CD14 expression were evaluated in 13 AIII-I patients, 13 PBC patients, 12 cirrhotic controls and 10 healthy subjects. TNF-alpha, TGF-beta and IFN-gamma were determined using ELISAs. Results: All apoptotic markers and CD14 were increased in AIII-I and PBC compared to controls (P < 0.0001). Fas + cells were positively correlated (P = 0.0001) with apoptotic cells in AIH-1 and PBC. TNF-alpha and IFN-gamma were higher in AIH-1 (P = 0.003 and P = 0.001) and PBC (P = 0.0001) compared to controls. No differences were found between the control groups. Conclusions: We demonstrate for the first time that the apoptotic process, macrophage activation and the production of cytokine suppressors of haematopoiesis in BMMCs from AIII-I and PBC patients are higher compared to controls. The Fas-FasL pathway is likely to be involved in the apoptotic process; the increased levels of selected cytokines may contribute to Fas-FasL stimulation. Cirrhosis appears unlikely to be the cause of the above findings. (c) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.