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Administration of Neutralizing Antibodies to Interleukin-6 (IL-6) Reduces Experimental Autoimmune Encephalomyelitis and Is Associated with Elevated Levels of IL-6 Bioactivity in Central Nervous System and Circulation

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Abstract

Background

We previously demonstrated the local production of the pleiotropic cytokine interleukin-6 (IL-6) in the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis.

Materials and Methods

To assess the role of IL-6 in autoimmune CNS inflammation, we administered neutralizing antibodies to IL-6 in the EAE model. Their effect was examined at the clinical and histopathological level. Levels of administered antibody and IL-6 bioactivity were followed in serum and cerebrospinal fluid (CSF).

Results

Systemically administered antibodies penetrated into the fluid CSF in animals in which EAE was induced. Administration of anti-IL-6 reduced the development of actively induced as well as adoptively transferred EAE and was associated with increased levels of IL-6 activity in the CSF and to a lesser extent in the serum. Anti-IL-6 was still effective when given 1 day before the onset of disease signs in adoptively transferred EAE. The disease-reducing effect of anti-IL-6 was also reflected at the pathological level by the absence of inflammatory infiltrates in the CNS.

Conclusions

Our study indicates that IL-6 plays an important role in autoimmune CNS inflammation. However, due to the complex nature of the in vivo interactions of administered antibodies, the disease-reducing effect of the anti-IL-6 antibodies could be caused by neutralization of IL-6 activity or by enhancement of IL-6 activity via induction of higher IL-6 levels in the CNS.

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Acknowledgments

This work was supported by the National Institutes of Health (NS18235) and by contributions from the Mendell Family, Hyman Abadi, the Fahnstock Family, and the Phil N. Allen Trust. DNAX is supported by Shering-Plough. KG was supported by the Belgian National Fund for Scientific Research (NFWO). The authors would like to thank A. Billiau (Leuven, Belgium) for helpful discussion.

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Authors and Affiliations

  1. Department of Neurology and Neurological Sciences, Beckman Center, Room B002, Stanford University Medical Center, Stanford, California, 94305-5429, USA

    Koenraad Gijbels, Stefan Brocke & Lawrence Steinman

  2. Department of Molecular Biology, DNAX Research Institute, Palo Alto, California, USA

    John S. Abrams

Authors
  1. Koenraad Gijbels
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  2. Stefan Brocke
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  3. John S. Abrams
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  4. Lawrence Steinman
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Contributed by I. Weissman on July 26, 1995.

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Gijbels, K., Brocke, S., Abrams, J.S. et al. Administration of Neutralizing Antibodies to Interleukin-6 (IL-6) Reduces Experimental Autoimmune Encephalomyelitis and Is Associated with Elevated Levels of IL-6 Bioactivity in Central Nervous System and Circulation. Mol Med 1, 795–805 (1995). https://doi.org/10.1007/BF03401894

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