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

Area of Science:

• Neuroimmunology
• Immunology
• Molecular Biology

Background:

• Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis.
• Myelin oligodendrocyte glycoprotein (MOG) is a key autoantigen in EAE.
• Interleukin-6 (IL-6) is a cytokine with pleiotropic immune functions.

Purpose of the Study:

• To investigate the role of IL-6 in EAE pathogenesis.
• To determine if IL-6 is required for the development of encephalitogenic T cell responses.
• To elucidate the mechanisms by which IL-6 influences EAE.

Main Methods:

• Induction of EAE in H-2b mice with intact or disrupted IL-6 genes using pMOG 35-55 peptide.
• Administration of recombinant IL-6 to IL-6-deficient mice.
• Histological analysis of brain and spinal cord tissues.
• Measurement of anti-MOG antibody levels.
• T cell line establishment and adoptive transfer experiments.

Main Results:

• IL-6+/+ mice developed chronic EAE, while IL-6-/- mice were resistant.
• Recombinant IL-6 administration restored EAE susceptibility in IL-6-/- mice.
• Perivascular inflammatory cell infiltration was absent in IL-6-/- mice and restored by IL-6.
• T cell lines from both genotypes were encephalitogenic, but induced less EAE in IL-6-deficient recipients.
• IL-6 appears crucial for local inflammatory processes in the central nervous system.

Conclusions:

• IL-6 is essential for the development of EAE.
• IL-6 plays a critical role in mediating inflammatory cell infiltration in the central nervous system during EAE.
• The resistance of IL-6-/- mice is not due to a lack of encephalitogenic T cells but rather impaired local inflammatory responses.