Induction of serum IL-18 withPropionibacterium acnesand lipopolysaccharide in phagocytic macrophage-inactivated mice

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Abstract
IL‐18, an important regulator of immune responses, is expressed in activated macrophages and also in nonimmune cells, such as keratinocytes and epithelial cells. Increased levels of serum IL‐18 are reported in patients with a wide variety of diseases, but it is unclear which type of cell is the major source of serum IL‐18. Here, we showed that the administration of liposomes encapsulating clodronate (Clo‐lip) in mice selectively depleted F4/80+ phagocytic macrophages in the liver and spleen. Serum levels of mature IL‐18 with 18 kDa were increased markedly in mice treated with Propionibacterium acnes and LPS, whereas administration of Clo‐lip and gadolinium chloride, another widely used macrophage inactivator, showed no obvious effect on serum IL‐18 levels, which were marginal in the liver, lung, and spleen and more pronounced in the intestines, especially in the duodenum. Treatment with P. acnes alone induced IL‐18 more than twofold in each organ, and P. acnes and LPS induced a marked increase in IL‐18 levels in the liver and spleen but decreased in the intestines. The administration of Clo‐lip showed only a marginal effect on the IL‐18 levels in these organs. Furthermore, serum levels of liver enzymes and TNF‐α and liver injury (necrotic change and granuloma formation) induced by P. acnes and LPS were reduced moderately by Clo‐lip. These results suggest that phagocytic macrophages do not actively contribute to the induction of serum IL‐18 and liver injury in mice treated with P. acnes and LPS.
Funding Information
  • Japan Society for the Promotion of Science (17390483, 18591995, 18791379)
  • Ministry of Education, Culture, Sports, Science and Technology, Japan