Alteration of thymus and of immune regulatory-antifibroblast factors in acute and chronic hepatic damage.
We studied in this paper the behavior of immunosuppressive and fibroblast proliferation inhibitory factors in the acute, chronic damage and cirrhotic alteration of the liver. We induced in LEW-rats acute hepatic necrosis by i.v. application of dimethylnitrosamine (DMNA: 35 mg/kg b.wt.) and by i.m. injection of CCl4 (1 ml/kg b.wt., twice a week). After 2-4 weeks we found chronic hepatic damage and after 8-10 weeks liver cirrhosis. As a control, untreated animals were used. Sera and liver factors were prepared from the animals and used for inhibition tests of fibroblast proliferation and MLC reaction. Furthermore, cell count and cell subpopulation of the thymus were determined by monoclonal antibodies (W3/25, OX-8). LF of untreated and DMNA-treated animals exhibited very strong unspecific inhibition effects of fibroblast proliferation and allogenic stimulation. However, with progression of hepatic damage (chronic hepatitis and cirrhosis) both suppressive abilities were gradually reduced. Normal sera showed very slight inhibition of allogenic stimulation but sera of animals with acute hepatic damage showed very strong inhibition. In the 2 weeks of CCl4 treatment, their inhibitory abilities were more than 40%, and with progression of hepatic damage they were gradually reduced. Normal sera or sera of animals with chronic hepatic damage could not suppress the fibroblast proliferation; however, sera of acute hepatic damage inhibited it very strongly. With chronic hepatic damage, the thymus gradually atrophied and, after 10 weeks of CCl4 treatment, it had atrophied completely. Thymocyte differentiation was found only in animals with acute hepatic damage. This suggests that factors which were liberated from the damaged hepatocytes caused differentiation of the thymocytes.
D000208:Acute Disease; D000818:Animals; D002251:Carbon Tetrachloride; D002452:Cell Count; D002455:Cell Division; D002908:Chronic Disease; D004128:Dimethylnitrosamine; D005347:Fibroblasts / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008110:Liver Extracts / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology*
D008110:Liver Extracts; D002251:Carbon Tetrachloride; D004128:Dimethylnitrosamine