Literature DB >> 18802703

Influence of humanized anti-IL-6R antibody, tocilizumab on the activity of soluble gp130, natural inhibitor of IL-6 signaling.

Misato Hashizume1, Masahiko Mihara.   

Abstract

Tocilizumab, humanized anti-IL-6R antibody is a novel anti-rheumatic drug. In the present study, we examined the influence of tocilizumab on the inhibitory activity of soluble gp130 (sgp130) against IL-6 signaling. BAF-h130 cells, human gp130 transfected mouse pro-B cell line, were cultured with the mixture with IL-6, sIL-6R and sgp130 for 72 h. BAF-h130 cells proliferated by the addition of both IL-6 and sIL-6R, but not IL-6 or sIL-6R alone. The proliferation induced by IL-6/sIL-6R complex was inhibited by sgp130 concentration-dependently. Tocilizumab inhibited IL-6/sIL-6R-induced cell proliferation. On the other hand, it did not affect the suppressive property of sgp130. To examine if tocilizumab can dissociate IL-6/sIL-6R/sgp130 complex, we established an ELISA system to detect IL-6/sIL-6R/sgp130 complex using anti-IL-6R coated ELISA plate. The results clearly indicated that ELISA system established was detectable IL-6/sIL-6R/sgp130 complex in a concentration dependent manner. Tocilizumab was added to IL-6/sIL-6R/sgp130 complex-fixed plate and then remaining IL-6/sIL-6R/sgp130 complexes on the plate were measured. The amount of IL-6/sIL-6R/sgp130 complexes on the plate was not changed by the addition of tocilizumab. In conclusion, tocilizumab exerts its inhibitory effect through the inhibition of IL-6R directly without affecting natural inhibitor sgp130.

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Year:  2008        PMID: 18802703     DOI: 10.1007/s00296-008-0703-8

Source DB:  PubMed          Journal:  Rheumatol Int        ISSN: 0172-8172            Impact factor:   2.631


  14 in total

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Authors:  M Hibi; M Murakami; M Saito; T Hirano; T Taga; T Kishimoto
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4.  Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family.

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Authors:  T Taga; Y Kawanishi; R R Hardy; T Hirano; T Kishimoto
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