Anti—tumor necrosis factor therapy abrogates autoimmune demyelination

TLDR

Anticytokine therapy may offer new therapeutic strategies for multiple sclerosis. The study aimed to determine whether anti‑TNF antibody could prevent experimental autoimmune encephalomyelitis (EAE) in SJL/J mice by targeting TNF in a model of MS. Anti‑TNF was administered intraperitoneally and also used to preincubate MBP‑sensitized T cells before adoptive transfer, allowing assessment of its effect on disease induction and T‑cell activity. Anti‑TNF treatment completely abrogated clinical and histopathological signs of EAE, did not impair the ability of MBP‑sensitized T cells or spleen cells to transfer disease, but prevented TNF production and thus inhibited the effector phase of demyelination.

Abstract

Abstract To define a role for the cytokine tumor necrosis factor (TNF) in immune‐mediated demyelination, the effect of anti‐TNF antibody was investigated with a form of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice induced by the adoptive transfer of myelin basic protein‐(MBP)‐sensitized T lymphocytes, an animal model of the human disease multiple sclerosis (MS). In three separate experiments, no mouse sensitized for EAE and then treated with anti‐TNF by intraperitoneal injection developed signs of central nervous system (CNS) disease. Examination of CNS tissue from anti‐TNF‐treated animals showed no pathological changes. CNS tissue from control animals demonstrated extensive inflammatory cell infiltration and demyelination. To test whether anti‐TNF therapy was inhibitory to encephalitogenic cells, preincubation of MBP‐sensitized T lymphocytes with anti‐TNF in vitro prior to injection into recipient mice was performed, and resulted in no diminution of their ability to transfer EAE. In addition, spleen cells from anti‐TNF‐ treated mice were capable of serial transfer of EAE, similar to spleen cells from control animals. However, spleen cells from anti‐TNF‐treated mice did not produce TNF on stimulation with MBP or concanavalin A. This study showed that anti‐TNF antibody can inhibit effectively the development of EAE by interfering with the effector, rather than the induction, phase of the disease. Anticytokine therapy may have important applications in the development of new therapeutic strategies for MS.