Interleukin‐6 functions in autoimmune encephalomyelitis: a study in gene‐targeted mice

The encephalitogenic peptide pMOG 35 – 55 from the myelin oligodendrocyte glycoprotein was used to induce experimental autoimmune encephalomyelitis (EAE) in H-2b mice with the interleukin-6 (IL-6) gene intact or disrupted. The IL-6+/+ mice developed a chronic form of EAE ascending paralysis, whereas the IL-6−/− mice were resistant to the disease. Injections of recombinant IL-6 following pMOG immunization induced severe disease in the IL-6−/− mice. Histological examination of brain and spinal cord sections showed that the perivascular infiltration of inflammatory cells evident in IL-6+/+ mice was absent in the IL-6−/− animals and could be restored by exogenous IL-6 administration. Anti-MOG antibody levels were much lower in the IL-6−/− mice, but were not restored to high levels by IL-6 injections which elicited the development of pMOG 35 – 55-induced EAE. T lymphocytes reactive to the pMOG 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 resistant 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 from IL-6+/+ mice is consistent with a function of IL-6 in the local perivascular inflammatory process.