Experimental allergic neuritis (EAN) was induced in normal and irradiated Lewis rats by passively transferring T cells sensitized to SP-26, a peptide fragment of P2 myelin protein. The recipients became sick 4-8 days post transfer and the degree of disability correlated directly with the dose of T cells. Smaller doses caused demyelination of nerve roots and sciatic nerves and larger doses produced more severe demyelination and significant axonal degeneration. Irradiated recipients developed similar clinical EAN and showed macrophage-mediated demyelination despite severe suppression of the host inflammatory response.

Lewis rat experimental allergic neuritis (EAN) was treated with the 21-aminosteroid, tirilazad mesylate (U-74006F). High doses of tirilazad mesylate, begun just before the onset of clinical signs, reduced the clinical and pathological severity of the disease. In rats immunized with a high dose of myelin, axonal degeneration was a major pathological feature. Tirilazad mesylate reduced the amount of axonal degeneration but had little effect on the other pathological features of EAN, such as inflammation and demyelination. Tirilazad mesylate may block axonal degeneration by inhibiting lipid peroxidation of axonal membranes. Inhibition of axonal degeneration is an important goal in the treatment of human neuropathies.

There is suggestive but inconclusive evidence for a contribution of T cells and antimyelin antibodies to the pathogenesis of the Guillain–Barré polyneuropathy. We have studied the potential synergism of cellular and humoral immunity in the adoptive transfer model of EAN. EAN was induced in Lewis rats by injecting varying doses of P2 peptide (SP26)‐sensitized T lymphocytes. Disease severity was dose‐dependent. The addition of intravenous GC‐AB to a subclinical dose of SP26‐sensitized T cells resulted in overt clinical disease and markedly enhanced demyelination. Intravenous injection of antibody alone had no effect. We conclude that activated neuritogenic T cells, while entering into peripheral nerves, alter the blood‐nerve barrier, which gives circulating demyelinating antibodies access to the endoneurium. The observations support the concept of a synergistic role of T‐cell autoimmunity and humoral responses in the inflammatory demyelination of Lewis rat EAN. © 1993 John Wiley & Sons, Inc.

In experimental allergic neuritis (EAN) severity of clinical disease and pathology correlate with the dose of antigen (Hahn et al., Lab Invest 59:115-125, 1988). To avoid axonal membrane contamination of the antigen, EAN was induced with a synthetic peptide, corresponding to residues 53-78 of bovine P2 myelin protein. Severity of EAN correlated with the dose of peptide in the inoculate. The relationship between demyelination, inflammation and axonal degeneration was studied. Low doses resulted in pure demyelination. Axonal degeneration occurred only with high doses of antigen and in association with very active mononuclear inflammation. The role of macrophages in producing axonal damage is discussed.