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Blood, 1 July 2001, Vol. 98, No. 1, pp. 235-237
BRIEF REPORT
Fas ligand-induced caspase-1-dependent accumulation of
interleukin-18 in mice with acute graft-versus-host
disease
Hisayuki Itoi,
Yoshihiro Fujimori,
Hiroko Tsutsui,
Kiyoshi Matsui,
Shizue Futatsugi,
Haruki Okamura,
Hiroshi Hara,
Toshikazu Hada,
Eizo Kakishita, and
Kenji Nakanishi
From the Second Department of Internal Medicine,
Department of Immunology and Medical Zoology, Third Department of
Internal Medicine, and Institute for Advanced Medical Sciences, Hyogo
College of Medicine, Nishinomiya, Japan; and Core Research for
Evolutional Science and Technology of Japan Science and Technology
Corporation, Tokyo, Japan.
Acute graft-versus-host disease (aGVHD), the fatal side
effects of bone marrow transplantation, was shown to be
accompanied by elevation of serum levels of interleukin 18 (IL-18). In
this study, the mechanism underlying the accumulation of IL-18 in aGVHD in mice was investigated. Lethally irradiated recipients having transplantation with H-2 disparate donor splenocytes demonstrated aGVHD
and contained markedly elevated serum levels of IL-18. In contrast,
recipients having transplantation with gld/gld spleen cells, which lack functional Fas ligand (FasL), contained only normal
ranges of IL-18, indicating FasL-mediated IL-18 release in aGVHD. The
wild-type hosts engrafted with caspase-1-deficient cells revealed
marked increases of IL-18 similar to those engrafted with wild-type
cells, whereas caspase-1-deficient recipients engrafted with wild-type
cells showed only a slight elevation of serum IL-18, indicating that
IL-18 elevation is derived from host cells in a caspase-1-dependent
manner. These results suggest FasL-mediated caspase-1-dependent IL-18
secretion in aGVHD in mice.
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