Knocking out IL-6 by vaccination
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Knocking out IL-6 by vaccination. / Galle, Pia; Hougs, Lotte; Barington, Torben; Svenson, Morten; Svejgaard, Arne; Thomsen, Allan Randrup; Bendtzen, Klaus; Hansen, Morten B.
I: European Journal of Immunology, Bind 34, Nr. 1, 2004, s. 291-300.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 34
SP - 291
EP - 300
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 1
ER -
ID: 9701330