Metallothionein in liver-biopsies from patients with different diseases

Metallothioneins (MT) are ubiquitous found in eukaryotic organism. MT have a potential for metal-storage and protect the cells against stress. On the genomic level, proinflammatory cytokines like interleukin-6 and transition metals like copper cause induction of MT. Therefore, an estimation of MT in liver-biopsies from patients with different diseases probably could help in identifying acute-phase reactions and processes which lead to increased copper. We investigated paraffin embedded liver biopsies from 170 patients and 13 control biopsies from cases of sudden death. Tissue was stained with a primary antibody against MT and a peroxidase technique was used to make results visible. A grading was performed using an immunoreactive score (IRS from 0-24) and by computer-aided measurement of the optical density (OD) of the stained tissue slides. Patients with cholestasis (IRS: 12.1 +/- 2.8, n = 11), autoimmune (10.6 +/- 3.1, n = 7) or inflammatory bowel diseases (IBD) (13.3 +/- 5.1, n = 4) and lymphoma (9.8 +/- 5.8, n = 21) showed marked increases in MT compared to the controls (5.2 +/- 2.8, n = 13). Patients with chronic hepatitis B or C or chronic alcoholic abuse had no elevation of MT. Furthermore, no correlation was found between histological damage and amount of MT except in cases of cholestasis, in which increased MT was observed. Results by OD confirmed the findings. In summary, we were able to demonstrate a clear increase of MT content in liver-biopsies in proinflammatory and cholestatic conditions. Marked elevation in patients with systemic diseases (like autoimmune-, IBD and lymphoma) seems to be best explained by an acute-phase induction of MT by proinflammatory cytokines. This could help in identifying these conditions in liver biopsies.