FK506 inhibits murine AA amyloidosis: possible involvement of T cells in amyloidogenesis.
OBJECTIVE
To determine the possibility that T cells represent a potential target for therapy in AA amyloidosis.


METHODS
AA amyloidosis was induced in C3H/HeN mice by concomitant administration of AgNO3 and amyloid-enhancing factor (AEF). Mice injected with AgNO3 and AEF received intraperitoneal injections of FK506 (2-200 microg/day). The degree of splenic amyloid deposition was determined by Congo red staining. Serum amyloid A (SAA), interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-a concentrations were measured by ELISA. AA amyloidosis was also induced in ICR mice by injection of Freund's complete adjuvant (FCA) and Mycobacterium butyricum without AEF. ICR mice injected with FCA and M. butyricum also received intraperitoneal injections of FK506 (200 microg/day) to eliminate the possibility that FK506 action might depend upon AEF activity in the amyloid formation. Amyloid deposition was also induced with and without AEF in severe combined immunodeficient (SCID) mice and nude mice to clarify the role of T cells in the mechanism of amyloid formation in AA amyloidosis.


RESULTS
FK506 treatment significantly reduced the amount of amyloid deposition and incidence of amyloidosis without reducing serum SAA and proinflammatory cytokine levels in the murine AA amyloidosis models with and without AEF. SCID mice and nude mice showed resistance to development of AA amyloidosis.


CONCLUSIONS
Our findings may provide a new therapeutic strategy for amyloidosis. The results suggested that T cells may play an important role in the mechanism of amyloid formation in AA amyloidosis.
Ueda
Mitsuharu
M
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
Ando
Yukio
Y
Nakamura
Masaaki
M
Yamashita
Taro
T
Himeno
Shingo
S
Kim
Jaemi
J
Sun
Xuguo
X
Saito
Shiori
S
Tateishi
Takiko
T
Bergström
Joakim
J
Uchino
Makoto
M
D000686:Amyloidosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D000685:Serum Amyloid A Protein / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D000685:Serum Amyloid A Protein; D016559:Tacrolimus