IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is induced by immunization with myelin components including myelin oligodendrocyte glycoprotein (MOG). Myelin-specific Th1 cells enter the central nervous system (CNS) via binding of very late antigen 4 (VLA-4) to the endothelial vascular cell adhesion molecule 1 (VCAM-1). In the present study, mice with a homologous disruption of the gene encoding IL-6 are found to be resistant to MOG-induced EAE as evidenced by absence of clinical symptoms, minimal infiltration of CD3+ T cells and monocytes into the CNS and lack of demyelination. The failure to induce EAE in IL-6-/- mice is not due to the absence of priming, since lymphocytes of immunized IL-6-/- mice proliferate in response to MOG and produce pro-inflammatory cytokines including IL-2 and IFN-gamma. However, in MOG-immunized IL-6-/- mice, serum anti-MOG antibody titers were found to be drastically reduced. This observation is unlikely to be responsible for resistance to EAE, because B cell-deficient (microMT) mice proved to be fully susceptible to the disease. A striking difference between MOG-immunized wild-type (wt) and IL-6-/- mice was the expression of endothelial VCAM-1 and ICAM-1, which were dramatically up-regulated in the CNS in wt but not in IL-6-/- mice. Taking into account recent studies on the role of VCAM-1 in the entry of Th1 cells into the CNS, the absence of VCAM-1 on endothelial cells in IL-6-/- mice may explain their resistance to EAE.
Eugster
H P
HP
Department of Internal Medicine, University Hospital Zurich, Switzerland. klimeuh@usz.unizh.ch
Frei
K
K
Kopf
M
M
Lassmann
H
H
Fontana
A
A
D000818:Animals; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015850:Interleukin-6; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1