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

J Hepatol. 2005 Mar;42(3):393-9. doi: 10.1016/j.jhep.2004.11.023.

Abstract

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 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.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Biomarkers / analysis
  • Bone Marrow Cells / pathology*
  • Cell-Free System
  • Cells, Cultured
  • Cytokines / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatitis, Autoimmune / blood
  • Hepatitis, Autoimmune / immunology*
  • Hepatitis, Autoimmune / pathology*
  • Humans
  • Interferon-gamma / analysis
  • Leukocytes, Mononuclear / pathology
  • Liver Cirrhosis, Biliary / blood
  • Liver Cirrhosis, Biliary / immunology*
  • Liver Cirrhosis, Biliary / pathology*
  • Male
  • Middle Aged
  • Reference Values
  • Transforming Growth Factor beta / analysis
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Biomarkers
  • Cytokines
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma