Pathological roles of granulomatous formation and Analysis of correlation with extrathymic T lymphocytes in Endotoxin-induced liver injury.

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P.acnes treatment induces Type-1 T cells in the liver by induction of IL-12 andII-18 production from kupffer cells. It is suggested that Kupffer cells is important roles in this process of granulomatoous formation. For the purpose of analysis of roles of Kupffer cells, we compared cytokine production by kupffer cells between P.acnes treatment and Schistosoma mansoni-soluble worm antigen preparation (SWAP) treatment. Non-treated Kupffer cells produce IL-6, IL-10, IL-12, IL-18, TNF-a by LPS.P.acnes-elicited Kupffer cells prduce IL-12, IL-18, TNF-a, IL-6 and IL-10 by LPS.On the other hand, SWAP-stimulated Kupffer cells produce IL-6, IL-10, IL-12, IL-18 and TNF-a by LPS.Interestingly, they produce IL-4, IL-13, IL-6 and IL-10 by SWAP.It is very unique events of IL-4 production by Kupffer cells from infected mice in respnse to SWAP.Acute graft-versus-host disease (aGVHD), fatal side effects of bone marrow transplantation, has been shown to be accompanied with evevation of serum levels of interleukin (IL)-18. Here, we investigated the mechanism underlying the accumulation of IL-18 in a GVHD in mice. Lethally irradiated recipients transplanted with H-2 disparate donor splenocytes confessed aGVHD and contained markedly elevated serum levels of IL-18. While recipients transplanted with gld/gld spleen cells that lack functional Fasligand (FasL), contained only normal ranges of IL-18, indicating FasL-medicated IL-18 release in aGVHD.The wild type hosts engrafed with caspase-1-deficent cells revealed marked increases of IL-18 level similar to those engrafted with wild type cells, while caspase-1-dependent recipients engrafted with wild type cells showed only slight elevation of serum IL-18, indicating that IL-18 elevation is derived from host cells in a caspase-1-dependent manner. These results suggested FasL-mediated caspase-1-dependent IL-18 secretion in a GVHD in mice.