Effect of treatment on clinical course of EAE in SJL/J mice. (a) Mice treated daily by s.c. injections days 1–10 posttransfer (dpt) with vehicle and 0.2, 0.6, or 2.0 mg/kg rhGGF2. Mean clinical score plotted for each group (n = 6). Differences between 2.0 mg/kg rhGGF2 and vehicle groups significant (P < 0.001). (b) Same animals as in a retreated on alternate days in the chronic phase of EAE from 33–53 dpt as follows: vehicle group retreated with vehicle; 2.0 mg/kg rhGGF2 group, with 0.02 mg/kg rhGGF2. Mean clinical score observed for each group (n = 3) until 67 dpt. Differences significant (P < 0.001). (c) Animals (n = 6) treated on alternate days from 21 to 79 dpt, using vehicle, 0.02 or 0.2 mg/kg. Observations conducted until 116 dpt. Mean clinical score plotted for each group (n = 6). (d) The cumulative relapse index of animals shown (c) that displayed a relapsing and remitting pattern of disease (n = 5, vehicle; n = 6, 0.02 mg/kg; and n = 6, 0.2 mg/kg). The cumulative relapse index for each group after 116 dpt was 1.40 (vehicle), 0.33 (0.02 mg/kg) and 0.66 (0.2 mg/kg). The reduction in relapse rate for each rhGGF2-treated compared with vehicle-treated group (100%) was 76% (0.02 mg/kg) and 53% (0.2 mg/kg). (P < 0.05, Mann–Whitney U test). (e) Treatment from 9 dpt, the peak of acute clinical signs, until 40 dpt on alternate days using vehicle, 0.02 or 1.0 mg/kg rhGGF2. Mean clinical score plotted for each group (n = 13 at 0 dpt) until end of observation period (n = 6, at day 66, and n = 4, at day 81). (f) Relapse index tabulated for animals in (e) that displayed a relapsing and remitting pattern (n = 10) observed from 21- 81 dpt. The cumulative relapse index for each group of relapsing-remitting animals at 81 dpt was 1.1 (vehicle), 0.50 (0.02 mg/kg) and 0.55 (1.0 mg/kg). The reduction in relapse rate for each rhGGF2 compared with vehicle-treated group (100%) was 58% (0.02 mg/kg) and 54% (1.0 mg/kg). Difference in cumulative relapse index between vehicle and each rhGGF2 treatment group significant (P < 0.05, Mann–Whitney U test).