Modulation of Anti-Tumor Necrosis Factor Alpha (TNF-?) Antibody Secretion in Mice Immunized with TNF-? Kinoid

Tumor necrosis factor alpha (TNF- alpha ) blockade is an effective treatment for patients with TNF- alpha -dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF- alpha kinoid, a heterocomplex of human TNF- alpha and keyhole limpet hemocyanin...

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Published in:Clinical and vaccine immunology 2012-05, Vol.19 (5), p.699-703
Main Authors: Assier, Eric, Semerano, Luca, Duvallet, Emilie, Delavallee, Laure, Bernier, Emilie, Laborie, Marion, Grouard-Vogel, Geraldine, Larcier, Patrick, Bessis, Natacha, Boissier, Marie-Christophe
Format: Article
Language:English
Subjects:
Adjuvants
Antibodies
Crohn's disease
Cyclophosphamide
Enzyme-linked immunosorbent assay
Hemocyanins
Immunosuppressive agents
Immunotherapy
Methotrexate
methylprednisolone
Psoriasis
Rheumatoid arthritis
Tumor necrosis factor- alpha
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Summary:Tumor necrosis factor alpha (TNF- alpha ) blockade is an effective treatment for patients with TNF- alpha -dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF- alpha kinoid, a heterocomplex of human TNF- alpha and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF- alpha . 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- alpha 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- alpha and anti-KLH antibody levels were assessed by enzyme-linked immunosorbent assay and the anti-TNF- alpha 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- alpha antibody production after TNF-K immunization. In contrast, the administration of cyclophosphamide (200 mg/kg) after immunization significantly reduced anti-TNF- alpha antibody titers and their neutralizing capacity.
ISSN:1556-679X
DOI:10.1128/CVI.05649-11