Figure 4

Long term treatment of EAE with anti-TNFR1 therapy is beneficial over an extended time frame. To prevent the occurrence of anti-drug antibodies, mice were treated with either H398, a mouse monoclonal antibody highly selective for human TNFR1 or control IgG on days 1, 4, 8 and 12 of manifest EAE. (A) H398-treated mice had reduced spinal cord deficits until approximately day 35 of EAE, at which point half the group received a further injection of 20 mg/kg H398 (re-treatment), and half received control IgG (no re-treatment) (relapse phase marked with light green bar). Those receiving H398 showed an improvement in disease severity which lasted approximately 20 days, after which mice underwent a further relapse (relapse phase marked with dark green bar) and were again treated with 20 mg/kg H398 or control IgG. Histopathological analyses of spinal cord were performed on all mice at day 85 of EAE and representative images shown from control IgG-treated mice (C,G,K,O), H398 + re-treatment (D,H,L,P) and H398 + no re-treatment (E,I,M,Q). Although demyelination (B–E) or T cell numbers (J–M) were not significantly affected by H398 re-treatment, mice which underwent a relapse following H398 treatment but no subsequent re-treatment had a significant elevation in the extent of axonal injury (F–I) and presence of activated microglia/macrophages (N–Q) than mice which underwent further H398 injections upon relapse (re-treated). ^*p < 0.05, ^**p < 0.01. n, control = 6; H398 + re-treatment = 3; H398 no re-treatment = 3. Scale bars = 200 µm.