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. 2000 Nov;59(Suppl 1):i21–i27. doi: 10.1136/ard.59.suppl_1.i21

Anti-interleukin 6 receptor antibody treatment in rheumatic disease

N Nishimoto, T Kishimoto, K Yoshizaki
PMCID: PMC1766618  PMID: 11053081

Abstract

Interleukin 6 (IL6) is a pleiotropic cytokine with a wide range of biological activities. IL6 transgene into mice gives rise to the abnormalities such as hyper-γ-globulinaemia, thrombocytosis, infiltration of inflammatory cells into the tissues, mesangial cell proliferation of the kidney as well as splenomegaly and lymphadenopathy, which are predictable by the biological functions of IL6 shown in vitro. Continuous overproduction of IL6 is observed in patients with some immune-inflammatory diseases such as Castleman's disease and rheumatoid arthritis that are frequently associated with similar abnormalities to those of IL6 transgenic mice, strongly suggesting the involvement of IL6 in the human diseases. Successful treatment of the model animals for immune-inflammatory diseases with anti-IL6 receptor (IL6R) antibody thus indicates the possible application of IL6 blocking agents to treat the IL6 related immune-inflammatory diseases of humans. In this review, the new therapeutic strategy for Castleman's disease and RA using humanised antibody to human IL6 receptor, MRA, is discussed.



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Figure 1  .

Figure 1  

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Schematic model of IL6 functions. IL6 is a pleiotropic cytokine with a wide range of biological activities.

Figure 2  .

Figure 2  

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Anti-IL6R antibody treatment suppressed the increase in serum IgG1 levels in IL6 transgenic mice. C57BL/6J human IL6 transgenic mice (tgm) were first intraveneously treated with 2 mg/body of rat antimouse IL6R antibody (MR16-1) at 4 weeks of age to induce tolerance to the mice against rat IgG, then subcutaneously treated with 100 µg/body twice weekly from 5 to 17 weeks of age. Serum IgG1 levels were analysed by ELISA.

Figure 3  .

Figure 3  

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Anti-IL6R antibody treatment inhibited the development of mesangial proliferative glomerulonephritis and lymphocytic interstitial pneumonia in IL6 transgenic mice. C57BL/6J human IL6 transgenic mice (tgm) were treated with rat antimouse IL6R antibody (MR16-1) similarly to that of figure 2. Left kidneys and lungs were removed and fixed with 20% neutral buffered formalin for histological examination.

Figure 4  .

Figure 4  

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Improvement in Castleman's disease by humanised anti-IL6R antibody treatment.

Figure 5  .

Figure 5  

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Improvement in RA by humanised anti-IL6R antibody treatment.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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