Induction of serum IL-18 with Propionibacterium acnes and lipopolysaccharide in phagocytic macrophage-inactivated mice.
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-alpha 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.
Nishioka
Takashi
T
Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Kuroishi
Toshinobu
T
Sugawara
Yumiko
Y
Yu
Zhiqian
Z
Sasano
Takashi
T
Endo
Yasuo
Y
Sugawara
Shunji
S
D000818:Animals; D005260:Female; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011425:Propionibacterium acnes / Q000187:drug effects / Q000276:immunology
D020382:Interleukin-18; D008070:Lipopolysaccharides