Document Detail


New therapeutic strategy for autoimmune and chronic inflammatory disease based on clinical results using IL-6 blocking therapy with a humanized anti-IL-6 receptor antibody
MedLine Citation:
PMID:  19483409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Remarkable clinical effects were observed by IL-6 blockage with a humanized anti IL-6 receptor antibody in patients with Castleman's disease, rheumatoid arthritis, and juvenile inflammatory arthritis. This evidence suggests that the hyper-function of IL-6 is an essential key cytokine in the pathogenesis of the above diseases, in which many cytokines, chemokines, and inflammatory molecules are activated. We found, for example, TNF-alpha blocking therapy showed a reduction of acute phase proteins, such as CRP and SAA, however, the IL-6 blockade induced not only reduction but also normalization of CRP and SAA serum levels. To elucidate this in vivo phenomenon, we analyzed the expression of cytokine inducing CRP and SAA mRNA with the intracellular signal transduction mechanism in vitro. The results, indicated that the IL-6 signal was essential though the activation of STAT3 for the induction and augmentation of CRP or SAA by the associated stimulation with TNF-alpha or IL-1. Recently, it is now known that IL-6 is a regulatory molecule in the induction of Th17 cells with TGF-beta. Therefore, IL-6 blockage may potentially improve autoimmune diseases, beginning with the pathogenic initiation phase. We believe that unknown pathogenic inflammatory phenomena can be clarified using this analytical strategy and cytokine blocking therapy. Furthermore, in the future we hope to induce complete remission of autoimmune diseases by using cytokine blockage freely.
Authors:
Kazuyuki Yoshizaki
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Publication Detail:
Type:  English Abstract; Journal Article; Review    
Journal Detail:
Title:  Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan     Volume:  129     ISSN:  0031-6903     ISO Abbreviation:  Yakugaku Zasshi     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-01     Completed Date:  2009-08-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413613     Medline TA:  Yakugaku Zasshi     Country:  Japan    
Other Details:
Languages:  jpn     Pagination:  667-74     Citation Subset:  IM    
Affiliation:
Center for Advanced Science and Innovation, Osaka University, Osaka, Japan. kyoshi@casi.osaka-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / therapeutic use*
Autoimmune Diseases / drug therapy*,  etiology
Chronic Disease
Humans
Inflammation / drug therapy*
Interleukin-6 / physiology
Receptors, Interleukin-6 / immunology*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Interleukin-6; 0/Receptors, Interleukin-6; 0/tocilizumab

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