Immunohistochemical study of tumor necrosis factor-alpha in acute liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

The effect of intravenous injection of Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS) on the distribution of tumor necrosis factor-alpha (TNF-alpha) in different organs have not previously been investigated. Immunohistochemistry and histological examination were employed in evaluating the distribution of TNF-alpha in the liver, spleen, lungs and bone marrow in rats injected intravenously with P. acnes followed by LPS 7 days later. Granulomas containing ED1-positive macrophages were observed in the liver 7 days after P. acnes injection. Subsequent LPS injection resulted in proliferation of ED1-positive macrophages in the sinusoids and coagulation necrosis of hepatocytes after 6 h. TNF-alpha was detected in ED2-positive macrophages (Kupffer cells) 1 day after P. acnes injection and in macrophages constituting the granulomas 7 days later, but prior to LPS injection. TNF-alpha was also detected in ED1-positive macrophages in the spleen, predominantly in the marginal zone. When granulomas were formed 7 days after P. acnes injection, TNF-alpha was observed in macrophages of the granulomas. TNF-alpha was also detected in macrophages of the granulomas found in the lung 1 day after P. acnes injection. No macrophages expressing TNF-alpha were found in the granulomas of bone marrow. The highest expression was in the liver al any time interval and in macrophages constituting granulomas. Our results suggest that the high expression of TNF-alpha in the liver results in selective hepatic necrosis. The expression of TNF-alpha in macrophages of the liver after P. acnes injection and the subsequent development of hepatic necrosis after LPS injection suggest that P. acnes acts as an inducer of TNF-alpha production in macrophages while LPS acts as a trigger for the release of TNF-alpha from macrophages. (C) 1997 Elsevier Science Ireland Ltd.