[Tumour necrotic factor (TNF) in the pathogenesis of liver necrosis in viral hepatitis and strategy for its prevention and treatment].
We determined serum and peripheral blood mononuclear cell (PBM) TNF activity in 8 healthy donors and 47 patients with hepatitis by using 3H-thymidine release method of Maennel et al. The serum TNF levels were significantly increased in chronic active hepatitis and subacute hepatic failure (13.8 +/- 6.3, and 19.4 +/- 3.9). Patients with serum bilirubin more than 10 mg/ml showed a higher serum TNF level than those with lower serum bilirubin. A significant elevation of TNF level was also observed in patients with positive endotoxemia or concurrent bacterial or viral infections. Experimental liver injury in Wistar rats induced by galactosamine (GLN) and LPS produced marked increase of serum TNF level and submassive liver necrosis. It is noteworthy that normal serum TNF and markedly ameliorated liver injury were observed in rats that received combined treatment with GLN, LPS and hepatopoietin (HPN), a low molecular peptide extracted from suckling porcine liver. In vitro, HPN also significantly suppressed TNF activity when it was co-incubated with PBM and LPS. An encouraging result was observed in preliminary clinical trial of HPN for the treatment of subacute liver failure. It suggests that Serum TNF appears to play an important role in the pathogenesis of liver injury from viral hepatitis and HPN seems to be a protection in liver injury against TNF activity.
Zhang
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D000293:Adolescent; D000328:Adult; D000818:Animals; D005260:Female; D006506:Hepatitis A / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006509:Hepatitis B / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006521:Hepatitis, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D014409:Tumor Necrosis Factor-alpha