Experimental liver injury induced by Propionibacterium acnes and lipopolysaccharide in macrophage colony stimulating factor-deficient osteopetrotic (op/op) mice

To clarify the involvement of growth and differention of liver macrophages mediated by macrophage colony-stimulating factor (M-CSF) in the liver injury induced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS), we used M-CSF-deficient osteopetrotic (op/op) mice. Seven days after injection of P. acnes, granulomas as well as the numbers of Thy-1.2-, Mac-1-, and ERMP-20-positive cells and F4/80-positive areas in the liver were significantly reduced in the op/op mice compared to the normal littermates. After injection of LPS, serum levels of alanine aminotransferase as well as concentrations of IL-1 beta and TNF-alpha in the serum and liver were significantly lower in the op/op mice than in the normal littermates, whereas the concentrations of IL-1 beta and TNF-alpha in the spleen were similar in op/op mice and normal littermates. These results suggest that M-CSF plays a partial but highly significant role in the development of liver injury induced by P. acnes and LPS via an intrahepatic increase of primed macrophages including those in granulomas, in response to P. acnes, which produce proinflammatory cytokines such as IL-1 beta and TNF-alpha.