 |
|
|
 |
FK506 Inhibits Murine AA Amyloidosis: Possible Involvement of T Cells in Amyloidogenesis
MITSUHARU UEDA, YUKIO ANDO, MASAAKI NAKAMURA, TARO YAMASHITA, SHINGO HIMENO, JAEMI KIM, XUGUO SUN, SHIORI SAITO, TAKIKO TATEISHI, JOAKIM BERGSTRÖM, and MAKOTO UCHINO ABSTRACT. 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 µg/day). The degree of splenic amyloid deposition was determined by Congo red staining. Serum amyloid A (SAA), interleukin 1ß (IL-1ß), 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 µg/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. Conclusion. 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. (First Release Sept 15 2006; J Rheumatol 2006;33:2260-70) Key Indexing Terms:
AA AMYLOIDOSIS From the Department of Neurology and Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto; and Clinical Medicine Section, Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto, Japan. Supported by grants from the Intractable Disease Division, Ministry of Health and Welfare, a Research Committee for Epochal Diagnosis and Treatment of Amyloidosis in Japan; and Grants-in-Aid for Scientific Research (B) 17390254 from the Ministry of Education, Science, Sports and Culture of Japan. M. Ueda, MD; T. Yamashita, MD, PhD, Assistant Professor; M. Uchino, MD, PhD, Professor, Department of Neurology; Y. Ando, MD, PhD, Associate Professor; S. Himeno, MMedSc; J. Kim, MPharm Sci; X. Sun, MD; S. Saito, MPharm Sci; T. Tateishi, MMedSc; J. Bergström, PhD, Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University; M. Nakamura, MD, PhD, General Manager, Clinical Medicine Section, Department of Clinical Medicine, National Institute for Minamata Disease. Address reprint requests to Dr. Y. Ando, Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan. E-mail: yukio@kaiju.medic.kumamoto-u.ac.jp Accepted for publication June 27, 2006.
|
