INTERLEUKIN-6 FUNCTIONS IN AUTOIMMUNE ENCEPHALOMYELITIS - A STUDY IN GENE-TARGETED MICE

The encephalitogenic peptide pMOG 35-55 from the myelin oligodendrocyt e glycoprotein was used to induce experimental autoimmune encephalomye litis (EAE) in H-2(b) mice with the interleukin-6 (IL-6) gene intact o r disrupted. The IL-6(+/+) mice developed a chronic form of EAE ascend ing paralysis, whereas the IL-6(-/-) mice were resistant to the diseas e. Injections of recombinant IL-6 following pMOG immunization induced severe disease in the IL-6(-/-) mice. Histological examination of brai n and spinal cord sections showed that the perivascular infiltration o f inflammatory cells evident in IL-6(+/+) mice was absent in the IL-6( -/-) animals and could be restored by exogenous IL-6 administration. A nti-MOG antibody levels were much lower in the IL-6(-/-) mice, but wer e not restored to high levels by IL-6 injections which elicited the de velopment of pMOG 35-55-induced EAE. T lymphocytes reactive to the pMO G antigen were recovered from lymph nodes of both types of mice and T cell lines could be established from both. Adoptive transfer of T cell lines from IL-6(+/+) mice induced EAE in the mice with the intact IL- 6 gene but less in the IL-6-deficient mice, indicating that the resist ant phenotype cannot be explained solely by lack of encephalitogenic T cells. The absence of cell infiltrates in the brain and spinal cords of IL-6(-/-) mice upon adoptive transfer of the pathogenic T cells fro m IL-6(+/+) mice is consistent with a function of IL-6 in the local pe rivascular inflammatory process.