Effects of FTY720 on rat lymphoid organs.
BACKGROUND
In this study, we examined the in vivo effect of FTY720 on rat thymus and spleen.


METHODS
Inbred male Lewis (RT-I(l)) rats, 5-weeks-old, received FTY720 (0.1, 1, or 10 mg/kg) by intramuscular injection into 1 of 4 limbs daily for 7 days. The rats were humanely killed at 1, 3, 5, or 7 days after starting administration of FTY720. The thymus and spleen were obtained for hematoxylin and eosin (HE) as well as immunoperoxidase staining using the antibodies OX8 (CD8), W3/25 (CD4), and OX6 (major histocompatibility complex class II).


RESULTS
HE staining revealed marked atrophy in the cortical region of the thymus among rats administered FTY720 at the dose of 10 mg/kg. The atrophy extended to the whole cortex. On day 7 of administration of FTY 720 (10 mg/kg), the medulla of the thymus showed relative expansion due to cells accumulation. Also, the spleens of FTY720-treated rats revealed an obvious reduction in the T-cell-dependent areas around the central artery. In conclusion, the immunosuppressive effect of FTY720 may be due to an inhibitory effect on T-cell emigration from the thymus to the periphery.
Takai
K
K
Department of Urology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. takai@yamaguchi-u.ac.jp
Takahara
S
S
Isoyama
N
N
Tsuchida
M
M
Matsumura
M
M
Kishi
Y
Y
Uchiyama
K
K
Naito
K
K
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001284:Atrophy; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology*; D008297:Male; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013110:Sphingosine / Q000031:analogs & derivatives; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine