title: Modulation of anti-tumor necrosis factor alpha (TNF-α) antibody secretion in mice immunized with TNF-α kinoid.
abstract: Tumor necrosis factor alpha (TNF-α) blockade is an effective treatment for patients with TNF-α-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-α kinoid, a heterocomplex of human TNF-α and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-α. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some immunosuppressive drugs on the generation of anti-TNF-α antibodies produced during TNF-K treatment. BALB/c mice were injected intramuscularly with TNF-K in ISA 51 adjuvant. Mice were also injected intraperitoneally with one of the following: phosphate-buffered saline, cyclophosphamide, methylprednisolone, or methotrexate. Anti-TNF-α and anti-KLH antibody levels were assessed by enzyme-linked immunosorbent assay and the anti-TNF-α neutralizing capacity of sera by L929 bioassay. Our results showed that current treatments used in rheumatoid arthritis, such as methylprednisolone and methotrexate, do not significantly alter anti-TNF-α antibody production after TNF-K immunization. In contrast, the administration of cyclophosphamide (200 mg/kg) after immunization significantly reduced anti-TNF-α antibody titers and their neutralizing capacity.
authors.affiliation: Sorbonne Paris, Cité Université Paris, Bobigny, France. eric.assier@univ-paris13.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Assier
authors.forename: Luca
authors.initials: L
authors.lastname: Semerano
authors.forename: Emilie
authors.initials: E
authors.lastname: Duvallet
authors.forename: Laure
authors.initials: L
authors.lastname: Delavallée
authors.forename: Emilie
authors.initials: E
authors.lastname: Bernier
authors.forename: Marion
authors.initials: M
authors.lastname: Laborie
authors.forename: Géraldine
authors.initials: G
authors.lastname: Grouard-Vogel
authors.forename: Patrick
authors.initials: P
authors.lastname: Larcier
authors.forename: Natacha
authors.initials: N
authors.lastname: Bessis
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D004344:Drug Incompatibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism*; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines