VASCULAR CHANGES AND DEMYELINATION INDUCED BY THE INTRANEURAL INJECTION OF TUMOR-NECROSIS-FACTOR

Several observations suggest that tumour necrosis factor (TNF) plays a role in demyelination, although direct evidence for this is lacking. We have examined ultrastructurally rat sciatic nerves injected with TN F-alpha or TNF-beta: the effects of the two cytokines were found to be qualitatively similar One day after injection nerves were oedematous and contained many inflammatory cells. Leucocytes were adherent to the walls of endoneurial vessels and sometimes were packed into the sub-e ndothelial layer apparently occluding the vascular lumen. Occasional m yelinated axons were associated with macrophages and showed signs of m yelin damage. By 3 days the inflammatory changes had diminished: some axons were degenerating or demyelinating. By 6-7 days the vascular cha nges had resolved, and the endoneurium contained significant numbers o f demyelinating and degenerating axons. Control nerves, which received injections of vehicle, showed no vascular changes and either no, or s ignificantly fewer degenerating or demyelinating axons. We conclude th at the intraneural injection of TNF produces inflammatory vascular cha nges within the endoneurium, together with demyelination and axonal de generation. We have also observed demyelination and degeneration in a preliminary study of the effects of TNF-alpha in mice. These findings may be relevant to the pathogenesis of demyelinating diseases such as Guillain Barre syndrome.