title: FK506 is superior to methotrexate in therapeutic effects on advanced stage of rat adjuvant-induced arthritis.
abstract: OBJECTIVE
  The anti-arthritic properties of FK506 were compared with methotrexate (MTX) in established adjuvant-induced arthritis (AIA) in rats.
  
  
  METHODS
  Female Lewis rats.
  
  
  METHODS
  Arthritic rats were orally administered with FK506 (1-5.6 mg/kg) and MTX (0.1-1 mg/kg) from days 15-24.
  
  
  METHODS
  Arthritis was induced by injection of Mycobacterium tuberculosis into the right hind footpad on day 0. Efficacy was determined on the basis of paw inflammation measured by paw volume and histological change, hyperalgesia and grip strength. Grip strength measurement was employed as an indication of function of paws in arthritic rats. Peripheral white blood cell (WBC) counts and thymus weights were measured, mainly as indicators of toxic side effects.
  
  
  RESULTS
  FK506 suppressed paw inflammation and hyperalgesia without toxic effects on WBC and thymus in established AIA. MTX slightly suppressed paw inflammation and hyperalgesia at the highest dose (1 mg/kg). Toxic effects were observed at lower doses than the effective treatment dose with MTX. Grip strength was found to decrease during development of AIA. FK506, but not MTX, treated rats recovered grip strength loss.
  
  
  CONCLUSIONS
  The results show that FK506 is more effective and less toxic than MTX in treating established AIA in rats.
authors.affiliation: Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, Osaka, Japan,
authors.forename: S
authors.initials: S
authors.lastname: Sakuma
authors.forename: F
authors.initials: F
authors.lastname: Nishigaki
authors.forename: K
authors.initials: K
authors.lastname: Magari
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
authors.forename: S
authors.initials: S
authors.lastname: Miyata
authors.forename: Y
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: T
authors.initials: T
authors.lastname: Goto
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005528:Foot / Q000473:pathology; D018737:Hand Strength; D006930:Hyperalgesia / Q000188:drug therapy / Q000473:pathology; D007958:Leukocyte Count; D008727:Methotrexate / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000627:therapeutic use*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
chemical_list: D018501:Antirheumatic Agents; D016559:Tacrolimus; D008727:Methotrexate