Figure 4

EC0746 demonstrates folate-receptor-specific anti-inflammatory activities in vivo. Starting on day 10 after arthritis induction, rats with developing adjuvant-induced arthritis (n = 5) were given a biweekly subcutaneous dosing regimen of EC0746 (250 nmol/kg) without or with a 500-fold molar excess of EC0923 as the folate competitor. For comparison purposes, methotrexate (MTX) (250 nmol/kg) was dosed orally following the same schedule as EC0746, and etanercept (10 mg/kg) was given subcutaneously on days 10, 13, 16, 19, and 22. Multiple endpoints are shown: (a) arthritis score; (b) change in body weight; (c) percentage increase in paw weight; (d) percentage increase in spleen weight; (e) representative X-ray images of arthritic hind paws taken using a Kodak Imaging Station; and (f) radiographic score of arthritic hind paws. *P < 0.05 when compared with the arthritic control group.