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

Abstract

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.

• Authors: H Itoi, Y Fujimori, H Tsutsui, K Matsui, S Futatsugi, H Okamura, H Hara, T Hada, E Kakishita, K Nakanishi
• Journal: Blood (Blood) Vol. 98 Issue 1 Pg. 235-7 (Jul 01 2001) ISSN: 0006-4971 [Print] United States
• PMID: 11418486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fas Ligand Protein
• Fasl protein, mouse
• Interleukin-18
• Membrane Glycoproteins
• Caspase 1

Topics

• Acute Disease
• Animals
• Caspase 1 (pharmacology)
• Disease Models, Animal
• Fas Ligand Protein
• Female
• Graft vs Host Disease (blood)
• Interleukin-18 (blood)
• Membrane Glycoproteins (pharmacology)
• Mice
• Mice, Mutant Strains
• Tissue Transplantation (adverse effects)