IL-6 plays a crucial role in the induction phase of myelin oligodendrocyte glucoprotein 35-55 induced experimental autoimmune encephalomyelitis.
We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active induction of EAE, but that the treatment of those mice with IL-6 during the preclinical phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1beta, IL-2, TNF-alpha, and IFN-gamma in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the induction phase, but might have little influence on the effector phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-gamma production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Thl to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the induction phase of EAE by modulating Th1/Th2 balance.
Okuda
Y
Y
Department of Neurology D-4, Osaka University Graduate School of Medicine, Suita, Japan.
Sakoda
S
S
Fujimura
H
H
Saeki
Y
Y
Kishimoto
T
T
Yanagihara
T
T
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology; D005260:Female; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology
D016207:Cytokines; D015850:Interleukin-6; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein