FK506 ameliorates spontaneous locomotor activity in collagen-induced arthritis: implication of distinct effect from suppression of inflammation.
FK506 (tacrolimus), an immunosuppressive drug, improves quality of life (QOL) for patients with rheumatoid arthritis (RA). However, the mechanism of FK506 behind the improvement in QOL is still uncharacterized. To explain the improvement of QOL by FK506, we investigated the effect of FK506 on spontaneous locomotor activity in rats with collagen-induced arthritis (CIA). CIA was induced in 7- to 8-week-old female Lewis rats by immunization with bovine type II collagen. After initiation of paw inflammation (paw swelling, histopathological analysis), CIA rats were therapeutically administered FK506 or methotrexate (MTX) from day 15. Therapeutic treatment with FK506 ameliorated spontaneous locomotor activity without suppressing paw inflammation in CIA rats from day 27. FK506 also improved hyperalgesia and grip strength from day 27. Therapeutic treatment with MTX did not improve spontaneous locomotor activity, and simultaneously did not recover hyperalgesia or grip strength in CIA rats. Our results indicate that spontaneous locomotor activity in CIA rats correlates mainly with hyperalgesia and muscle strength, but not paw inflammation, implying that therapeutic treatment with FK506 ameliorates spontaneous locomotor activity via improvement of hyperalgesia and muscle strength in CIA rats.
Sasakawa
Tatsuya
T
Department of Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6 Kashima, Osaka 532-8514, Japan. tatsuya_sasakawa@po.fujisawa.co.jp
Sasakawa
Yuka
Y
Ohkubo
Yoshitaka
Y
Mutoh
Seitaro
S
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005270:Femur Head / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D011509:Proteoglycans; D016559:Tacrolimus; D008727:Methotrexate