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 Tcell lines could be established from both. Adoptive transfer of Tcell 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 Tcells. The absence of cell infiltrates in the brain and spinal cords of IL-6-/- mice upon adoptive transfer of the pathogenic Tcells from IL-6+/+ mice is consistent with a function of IL-6 in the local perivascular inflammatory process.
Mendel
I
I
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Katz
A
A
Kozak
N
N
Ben-Nun
A
A
Revel
M
M
D019264:Adoptive Transfer; D000818:Animals; D000954:Antigens, Surface / Q000008:administration & dosage; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D018390:Gene Targeting; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D001323:Autoantibodies; D015850:Interleukin-6; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011994:Recombinant Proteins