Knocking out IL‐6 by vaccination

Inappropriate expression of IL‐6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL‐6‐receptor interactions. Here we present a simple and highly effective approach based on vaccination with a p...

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Bibliographic Details
Published in:European journal of immunology 2004-01, Vol.34 (1), p.291-300
Main Authors: Galle, Pia, Hougs, Lotte, Barington, Torben, Svenson, Morten, Svejgaard, Arne, Thomsen, Allan R., Bendtzen, Klaus, Hansen, Morten B.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies - immunology
Autoimmunity
Female
Humans
Inflammation
Interleukin-6 - analogs & derivatives
Interleukin-6 - immunology
Interleukin‐6
Mice
Molecular Sequence Data
Protein Structure, Tertiary
Tolerance
Vaccination
Vaccines - immunology
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Summary:Inappropriate expression of IL‐6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL‐6‐receptor interactions. Here we present a simple and highly effective approach based on vaccination with a pool of specifically mutated IL‐6 analogues to induce a neutralizing IL‐6 antibody responsein mice. Judged by the ability of the analogues to bind to heterologous anti‐IL‐6 antibodies and cellular IL‐6 receptors the IL‐6 analogues seemed to have a three‐dimensional structure comparable to that of wild‐type IL‐6. Injection of them broke self‐tolerance and induced an immune response to IL‐6, presumably because of the amino acid differences between the analogues and wild‐type IL‐6. This resulted in a long‐lasting anti‐IL‐6 antibody‐mediated IL‐6 deficiency that blocked experimentally induced IL‐6‐mediated pathology.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200324338