Knocking out IL-6 by vaccination

TY - JOUR

T1 - Knocking out IL-6 by vaccination

AU - Galle, Pia

AU - Hougs, Lotte

AU - Barington, Torben

AU - Svenson, Morten

AU - Svejgaard, Arne

AU - Thomsen, Allan Randrup

AU - Bendtzen, Klaus

AU - Hansen, Morten B

N1 - Keywords: Amino Acid Sequence; Animals; Antibodies; Female; Humans; Interleukin-6; Mice; Molecular Sequence Data; Protein Structure, Tertiary; Vaccines

PY - 2004

Y1 - 2004

N2 - 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 response in 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.

AB - 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 response in 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.

U2 - 10.1002/eji.200324338

DO - 10.1002/eji.200324338

M3 - Journal article

C2 - 14971055

SN - 0014-2980

VL - 34

SP - 291

EP - 300

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 1

ER -