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


METHODS
Apoptotic markers and CD14 expression were evaluated in 13 AIH-1 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 AIH-1 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 AIH-1 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.
Tsikrikoni
Aikaterini
A
Research Laboratory of Internal Medicine, Department of Medicine, Faculty of Health Sciences, Medical School, University of Thessaly, Larissa, Greece.
Kyriakou
Despina S
DS
Rigopoulou
Eirini I
EI
Alexandrakis
Michael G
MG
Zachou
Kalliopi
K
Passam
Freda
F
Dalekos
Georgios N
GN
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000473:pathology*; D002474:Cell-Free System; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D016207:Cytokines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma