Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atlizumab [Actemra, MRA] is a humanised anti-interleukin-6 receptor monoclonal antibody. It was originated by the Japanese company Chugai Pharmaceutical and is being developed for the treatment of rheumatoid arthritis, Crohn's disease, multiple myeloma and the lymphoproliferative disorder giant lymph node hyperplasia (Castleman's disease). In October 2002, a majority share (50.1%) in Chugai Pharmaceutical was acquired by Roche. Nippon Roche was merged into Chugai Pharmaceutical, which is now Roche's exclusive pharma representative in Japan. The relationship between Chugai Pharmaceutical and Roche has been defined through a jointly agreed governance agreement, by which Chugai Pharmaceutical will be an autonomously managed company. Chugai Pharmaceutical is now Roche's exclusive pharma representative in Japan and will have rights to develop and market Roche products in Japan. As part of the transaction, Roche gained rights of first refusal for licencing, marketing or co-developing any Chugai Pharmaceutical products which are available for partnering. In the first quarter of 2003, Chugai Pharmaceutical and Roche formed an agreement to co-develop and co-promote atlizumab. The companies will co-promote the drug in the UK, France and Germany. Roche will co-develop and promote atlizumab worldwide, except in Japan, South Korea and Taiwan. Chugai Pharmaceutical has retained co-promotion rights in the US, Italy and Spain. Atlizumab completed phase II development for giant lymph node hyperplasia in Japan in 2002, where it has been granted orphan drug status. In April 2003, a regulatory filing was submitted in Japan for use of atlizumab in the treatment of giant lymph node hyperplasia. In May 2000, Chugai Pharmaceutical and the US company Protein Design Labs reached an agreement whereby Chugai Pharmaceutical will receive nonexclusive, worldwide licences for an undisclosed number of its antibody targets under Protein Design Labs' antibody humanisation patents. One of the targets included is the human interleukin-6 receptor. Chugai Pharmaceutical will pay Protein Design Labs 6.04 million US dollars in signing and licencing fees. Chugai Pharmaceutical will also pay annual maintenance fees and royalties on any future product sales.
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PMID:Atlizumab: anti-IL-6 receptor antibody-Chugai, anti-interleukin-6 receptor antibody-Chugai, MRA-Chugai. 1449 66

To characterize the biological activity of tocilizumab, a humanized anti-human interleukin-6 receptor (IL-6R) monoclonal antibody, we examined its binding activity to both soluble IL-6R (sIL-6R) and membrane bound IL-6R (mIL-6R) and its neutralizing activity to other IL-6 family cytokines. ELISA assay demonstrated that tocilizumab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose-dependent manner. The dissociation constant (Kd value) for IL-6R was determined to be 2.54+/-0.12 nmol/L by Scatchard analysis. In addition, tocilizumab had the ability to dissociate IL-6 and sIL-6R from their preformed complex. The immune complex of tocilizumab and sIL-6R did not transmit signaling. Moreover, tocilizumab suppressed the IL-6/sIL-6R complex-induced proliferation of human gp130-transfected cell, BAF-h130. In addition, tocilizumab had the ability to bind to human IL-6R expressing COS-7 cells and to suppress the growth of the IL-6-dependent myeloma cell line, KPMM2. Finally, to analyze the specificity of this antibody, the effects on signal transduction of IL-6 family cytokines such as interleukin-11 (IL-11), oncostatin M (OSM), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF) were examined using murine transfectant cell lines (BaF/IL-6R, BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR) that proliferate depending on IL-6, IL-11, OSM, LIF and human CNTF, respectively. Tocilizumab inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by their corresponding cytokines. These lines of evidence indicate that tocilizumab is able to bind to both sIL-6R and mIL-6R and to inhibit IL-6 binding to its receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and mIL-6R, but not block the signaling of other IL-6 family cytokines.
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PMID: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. 1610 23

We report an excellent clinical response to treatment with a humanized anti-interleukin-6 receptor antibody, tocilizumab, in a patient with progressive amyloid A (AA) amyloidosis complicating very active juvenile idiopathic arthritis. Treatment with tocilizumab immediately normalized the serum AA (SAA) level, and subsequently all of the clinical symptoms of AA amyloidosis disappeared. Serial gastrointestinal biopsy specimens showed marked lasting regression of AA protein deposits. The patient's functional ability score improved dramatically, she maintains her mobility, and she has regained her previous quality of life. Tocilizumab appears to have an excellent ability to suppress SAA levels and could therefore be an important therapeutic strategy in AA amyloidosis secondary to rheumatic diseases.
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PMID:Successful use of a humanized anti-interleukin-6 receptor antibody, tocilizumab, to treat amyloid A amyloidosis complicating juvenile idiopathic arthritis. 1694 31

In the treatment of rheumatic diseases such as rheumatoid arthritis (RA) or systemic onset juvenile idiopathic arthritis (soJIA), new therapies targeting pro-inflammatory cytokines have been developed. IL-6 is a pleiotropic cytokine with a wide range of biological activities including a pro-inflammatory mediator activity. Overproduction of IL-6 has been reported to be pathologically involved in the rheumatic diseases and, therefore, blockade of IL-6 actions may improve the disease. Tocilizumab, a humanized monoclonal antibody against human interleukin-6 receptor (IL-6R), inhibits IL-6 binding to IL-6R and specifically interferes with IL-6 actions. Castleman's disease is an atypical lymphoproliferative disorder caused by the overproduction of IL-6. Tocilizumab therapy improves immunological and hematological abnormalities as well as systemic inflammatory symptoms including wasting. This translational study also confirmed the pathological significance of IL-6 in the disease. RA is a representative autoimmune inflammatory disease characterized by bone and cartilage destruction in multiple joints. Since IL-6 also plays pathological roles in RA, tocilizumab therapy has been introduced to the patients with refractory disease and has shown a strong therapeutic effect. Besides Castleman's disease and RA, tocilizumab has been shown to be effective for patients with soJIA and Crohn's disease. Tocilizumab treatment is generally well tolerated and safe. Therefore, tocilizumab can be a promising therapeutic agent for the rheumatic diseases in which IL-6 overproduction is pathologically involved.
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PMID:Anti-interleukin-6 receptor antibody therapy in rheumatic diseases. 1721 83

Interleukin-6 (IL-6) plays pathological roles in promoting autoimmune reactions and chronic inflammation as well as destruction of bone and cartilage in rheumatoid arthritis (RA). Humanized anti-human IL-6 receptor antibody, tocilizumab, specifically recognizes human IL-6 receptor and inhibits IL-6 actions. Tocilizumab has been shown to ameliorate the disease activity of RA in the clinical trials. Tocilizuamb can be a new therapy based on the pathology of RA.
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PMID:[Clinical benefits of anti-human IL-6 receptor antibody therapy]. 1740 86

We report three cases of multicentric Castleman's disease (MCD) successfully treated with anti-interleukin-6 receptor antibody (tocilizumab). Tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. In each case, tocilizumab alleviated symptoms, including generalized fatigue, pyrexia, and alleviated biochemical abnormalities, including anemia, hypoalbuminemia, hypergammaglobulinemia, and increased C-reactive protein (CRP). Side effects included hypercholesterolemia, acute pyelonephritis, mild inflammation of the parotid glands, and upper respiratory system inflammation. Other severe side effects were not observed. These results indicate that tocilizumab is effective for the treatment of MCD. This is the first report on tocilizumab efficacy for Castleman's disease after approval for use for Castleman's disease.
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PMID:Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease. 1754 Dec 33

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune response and inflammatory reaction. IL-6 has been shown to play pathological roles in the autoimmune reaction, inflammation, and joint destruction in rheumatoid arthritis, and, therefore, an agent blocking IL-6 actions can be a therapeutics of the disease. Tocilizumab is a humanized anti-human IL-6 receptor antibody designed using genetic engineering technology and the first therapeutic monoclonal antibody developed in Japan. Tocilizumab specifically blocks IL-6 actions and ameliorates the diseases with IL-6 overproduction. It has been clinically developed for rheumatoid arthritis and shown to be effective not only for improving signs and symptoms but also for preventing joint destruction of the disease. In this chapter, immunopharmacology and clinical utility of tocilizumab in rheumatoid arthritis is addressed.
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PMID:[Humanized anti-human IL-6 receptor antibody, tocilizumab]. 1764 35

Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates immune responses and inflammatory reactions. Overproduction of IL-6 has been shown to play a role in inflammatory autoimmune diseases such as rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA) and, therefore, an agent blocking IL-6 actions can be a therapy of these diseases. IL-6 belongs to a cytokine family, which shares the cytokine receptor subunit glycoprotein (gp) 130. This family also includes IL-11, oncostatin-M, and leukemia inhibitory factor (LIF). In the IL-6 receptor (IL-6R) system, both a membrane-bound IL-6R and a soluble form of IL-6R are able to mediate IL-6 signals into the cells through the interaction of gp130. Tocilizumab is a humanized antihuman IL-6 receptor antibody designed using genetic engineering technology. Tocilizumab recognizes both the membrane-bound and the soluble form IL-6R and specifically blocks IL-6 actions. Tocilizumab is expected to ameliorate the autoimmune inflammatory diseases with IL-6 overproduction and has been clinically developed as a therapeutic agent for RA, systemic-onset and articular types of JIA, Crohn's disease, etc. Tocilizumab has been shown to be effective not only for improving signs and symptoms but also for preventing joint destruction of RA. Immunopharmacology and clinical benefit of tocilizumab in RA is addressed.
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PMID:Humanized antihuman IL-6 receptor antibody, tocilizumab. 1807 45

We examined if tocilizumab, humanized anti-interleukin-6 receptor (IL-6R) antibody, can ameliorate joint swelling after the onset of arthritis in collagen-induced arthritis (CIA). CIA was induced by the immunization of bovine type II collagen in female cynomolgus monkeys. Tocilizumab (30 mg/kg) was administered weekly for 4 weeks after the onset of arthritis. Swelling of 16 proximal interphalangeal (PIP) joints of hands and feet was monitored by measuring the longitudinal and transverse axes of PIP joints and the oval area of each PIP was calculated. Serum was collected once a week after tocilizumab injection and blood chemistry, IL-6, soluble IL-6R (sIL-6R), and anti-tocilizumab antibody were measured. At the end of study, histopathological examination of joints was performed. Tocilizumab clearly reduced joint swelling in all animals without anti-tocilizumab antibody. Histopathological study showed significant decrease in the infiltration of neutrophils into inflamed joints was observed in tocilizumab-treated animals. In conclusion, tocilizumab improved established arthritis in monkey and monkey CIA model is useful for the analysis of anti-arthritic effect of tocilizumab.
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PMID:Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorates joint swelling in established monkey collagen-induced arthritis. 1852 48

Cytokines such as TNF-alpha and IL-1beta play key roles in driving the inflammation and synovial cell proliferation that characterize rheumatoid arthritis (RA) joint destruction. It is, therefore, not surprising that therapies for RA have targeted these cytokines. While blockade of TNF-alpha or IL-1beta has been efficacious for many patients with RA, adequacy and maintenance of response are not universal, and increased risk of adverse events such as infections and malignancy remain a concern. Therefore, new targets in the treatment of RA continue to be examined. As interleukin-6 (IL-6) has been implicated in the pathogenesis of RA, blockade of its activity is of both scientific and clinical interest. Tocilizumab has been assessed in a number of studies in recent years, mainly in patients with rheumatoid arthritis. Data from randomized controlled clinical trials demonstrate the effectiveness of tocilizumab in improving the signs and symptoms of RA. In addition, it appears that such inhibition of IL-6 can have positive effects on functional status, an important outcome for RA patients. Finally, data suggest that treatment with this agent may also inhibit the progression of disease as assessed radiographically. Data from recent studies will help to refine the ultimate use of this novel approach to treatment, and help clinicians to optimize therapy using this approach.
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PMID:[The role of interleukin-6 in rheumatoid arthritis]. 1871 59


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