Fas ligand-induced caspase-1-dependent accumulation of interleukin-18 in mice with acute graft-versus-host disease

Itoi, H Fujimori, Y Tsutsui, H Matsui, K Futatsugi, S Okamura, H Hara, H Hada, T Kakishita, E Nakanishi, K

H. Itoi et al., Fas ligand-induced caspase-1-dependent accumulation of interleukin-18 in mice with acute graft-versus-host disease, BLOOD, 98(1), 2001, pp. 235-237

23

INGLESE

Article

Hematology,"Cardiovascular & Hematology Research

BLOOD

0006-4971 → ACNP

98

1

2001

235 - 237

ISI

0006-4971(20010701)98:1<235:FLCAOI>2.0.ZU;2-L

Acute graft-versus-host disease (aGVHD), the fatal side effects of bone mar row transplantation, was shown to be accompanied by elevation of serum leve ls of interleukin 18 (IL-18), In this study, the mechanism underlying the a ccumulation of IL-18 in aGVHD in mice was investigated. Lethally irradiated recipients having transplantation with H-2 disparate donor splenocytes dem onstrated aGVHD and contained markedly elevated serum levels of IL-18, In c ontrast, recipients having transplantation with gld/gld spleen cells, which lack functional Fas ligand (FasL), contained only normal ranges of IL-18, indicating Fast-mediated IL-18 release in aGVHD, The wild-type hosts engraf ted with caspase-1-deficient cells revealed marked increases of IL-18 simil ar to those engrafted with wild-type cells, whereas caspase-1-deficient rec ipients engrafted with wild-type cells showed only a slight elevation of se rum IL-18, indicating that IL-18 elevation is derived from host cells in a caspase-1-dependent manner. These results suggest Fast-mediated caspase-1-d ependent IL-18 secretion in aGVHD in mice. (C) 2001 by The American Society of Hematology.