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Interleukin (IL)-18 is one of the inflammatory cytokine which is expressed not only in activated macrophages but also in non-immune cells, such as keratinocytes and epithelial cells. It is unclear which type of cell is the major source of serum IL-18. We showed that serum levels of IL-18 were increased in mice treated with Propionibacterium acnes and lipopolysaccharide (LPS), whereas, administration of clodronate-liposomes (Clo-lip) to induce depletion of macrophages showed no obvious effect on IL-18 levels. IL-18 levels were marginal in the liver, lung and spleen. Treatment with P. acnes alone induced IL-18 in each organ, and P. acnes and LPS induced increase in IL-18 levels in the liver and spleen, but decrease in the intestines. The administration of Clo-lip in mice showed only a marginal effect on the IL-18 levels in the organs. These results suggest that IL-18 expressed in keratinocytes/epithelial cells contributes to serum IL-18 levels. [ABSTRACT FROM AUTHOR]