p38 MAPK blockade ameliorates EAE. (A) Clinical course of EAE in B6 mice immunized with 2× MOG35-55-CFA treated with either carrier or SB203580. (B) Clinical course of EAE in B6 mice immunized with 2× MOG35-55-CFA treated with either carrier or SB203580 starting on day 0 (first arrow), treatment terminated on day 31 (arrow with cross), and retreated from day 41 through day 60 (second arrow). (C) Clinical course of EAE in B6 mice immunized with 2× MOG35-55-CFA and randomly selected for treatment with either carrier or SB203580 on reaching a clinical score ≥ 1. (D) Remitting-relapsing EAE course in SJL mice immunized with 2× PLP135-151-CFA. After the initial episode of EAE and after 2 days of remission defined as a score of 0 for a minimum of 2 days, mice were treated with either carrier or SB203580 (arrow). The significance of the differences between the clinical courses of disease in panels A and B (day 0-day 40), and panel C was calculated by regression analysis and best-fit curves are shown. In pane D, 2-way ANOVA followed by Bonferroni posthoc comparisons was used to determine significant differences in disease severity for individual days (*P = .01, **P = .001).