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

被引:13
作者
Assier, Eric [1 ]
Semerano, Luca [1 ,2 ]
Duvallet, Emilie [1 ]
Delavallee, Laure [1 ]
Bernier, Emilie [3 ]
Laborie, Marion [3 ]
Grouard-Vogel, Geraldine [3 ]
Larcier, Patrick [3 ]
Bessis, Natacha [1 ]
Boissier, Marie-Christophe [1 ,2 ]
机构
[1] Cite Univ Paris, Bobigny, France
[2] Grp Hosp Avicenne Jean Verdier Rene Muret, AP HP, Serv Rhumatol, Bobigny, France
[3] Neovacs SA, Paris, France
关键词
RHEUMATOID-ARTHRITIS; CELL; METHOTREXATE; VACCINATION; MODEL; INHIBITION; INFLIXIMAB; THERAPY; AGENTS;
D O I
10.1128/CVI.05649-11
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:699 / 703
页数:5
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