IL-6 induces hepatic inflammation and collagen synthesis in vivo

Abstract

SUMMARY IL-6 regulates the synthesis of a broad spectrum of acute phase proteins in the liver. Also, it is involved in the pathogenesis of many fibrogenic diseases. To study ihe inflammatory effects of IL-6 on the in vetro human rIL-6, produced in Escherichia coli. was injected intraperitoneally into rats (25 μ/100 g body weight). The major fractopm of injected 11-6 was accumulated in the liver within 40 min, and the number of platelets was increased during 72 hafter injection. After 5 weeks of injection. the levels of serum glutamine pyruvic transaminase (GPT) and glutamic oxaloacctic transaminase (GOT) were not changed, but they were significantly elevated at 13 weeks of treatment. Meanwhile, scrum albumin levels were slightly decreased compared with those of controls. The same phenomena were observed in carbon tetrachloride-treated rats. Collagen synthesis was increased in the liver tissues and in the culture supernatants of hepatic lipocyles isolated from the rats treated with lL-6for 13 weeks. Histological analysis correlated well with biochemical analysis. At 5 weeks of treatment, only mild pathological changes were observed, but severe hepatocyte necrosis and the accumulation of fibres in necrotic area were developed in the liver of IL-6-treated rats after 13 weeks of treatment, confirming that hepatic inflammation and fibrosis were developed. IL-6 activities in the sera and in the culture supernatants of lipocytes from IL-6-treated rats were elevated compared with those in controls. These biochemical and pathological data indicate that IL-6 can induce hepatic inflammation, and it has important roles in the pathogenesis of fibrosis and diseases of the liver in vivo. In addition, these results will provide useful information for ihc clinical trials of IL-6.