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IL-6シグナル伝達阻害による新しい治療法の開発

通过抑制 IL-6 信号传导开发新的治疗方法

基本信息

批准号：
08839016
负责人：
吉崎和幸
金额：
$ 1.54万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至无数据
项目状态：
已结题

项目摘要

ヒト型化抗IL-6受容体抗体を用いて、IL-6の異常産生がその病態の中心的役割を果たす疾患、即ちCastleman病、慢性関節リウマチ(RA)を対象としてIL-6シグナル伝達を阻害する新しい治療法を試みた。multicentric typeのCastleman病患者6人を対象とし、インフォームドコンセントを得たのち、先進医療審査会の許可のもとに治療を試みた。これらの患者は、発熱、全身倦怠感、結節性紅斑等に加え、CRP,フィブリノーゲンの上昇、低アルブミン血症、γグロブリン血症、血小板増多、貧血等の異常所見を有したが、ヒト型化抗IL-6受容体抗体(50mg/body)を週1回または2回投与したところ、臨床症状のみならず、検査値の異常も改善した。特に慢性炎症による貧血は、CRP正常化後に改善し始め2ヵ月後にはHb値で2〜3g/dlの改善を認めた。RAの患者においても同様に、11人の患者にヒト型化抗IL-6受容体抗体を投与した。RAの患者においてもCRPの陰性化とフィブリノーゲンの正常化にわずかに遅れて、朝のこわばり、握力、圧痛関節数、腫脹関節数の著明は改善が認められた。また炎症の改善に伴い、ヘモグロビンの正常化、リウマチ因子の低下がみられ、また免疫グロブリンは高い値を示した症例でのみ改善傾向が認められた。抗体の投与中、肝機能、腎機能などへの影響は全く認められず、最長10ヶ月間の継続投与を行ったが治療効果が変わらなかった。但し、今までに治療を行った17例のうち1例において抗デイオタイプ抗体の出現を認め、抗体の投与を中止した。IL-6の多彩な生理機能や、種種の病態における役割が明らかになり、臨床への応用も可能になった。今回、IL-6が実際にこれらの疾患の病体に関与していることが確認されると同時に、IL-6のシグナル伝達阻害が病態をふまえた新しい治療法として有用であることがわかった。

Typed anti-IL-6 receptor antibodies were used to treat diseases such as Castleman disease, chronic infectious diseases (RA) in the center of infectious diseases, such as Castleman disease, chronic infectious diseases (RA). The results showed that there was no significant difference between the two groups. Six patients with multicentric type's Castleman disease were diagnosed with clinical symptoms, clinical symptoms, and advanced medical treatment. The number of patients, symptoms, general tiredness, resultant plaque and other symptoms, CRP It is common to see some diseases, such as high blood pressure, low blood pressure, gamma-ray blood disease, thrombocytopenia, thrombocytopenia, blood, and so on. It is often seen that anti-IL-6 receptor antibodies (50mg/body) are reinjected back in 1 time and 2 times in the first time. Two months after the normalization of CRP, the symptoms of chronic inflammation, Hb and 2~3g/dl were improved. Patients with RA were infected with the same antibody, and 11 patients with hepatitis B were infected with anti-IL-6 receptor antibody. In patients with RA, there is an indication of improvement in the number of pain, grip strength, pain, and the number of pain in patients with RA. The symptoms of inflammation were improved, normalized, decreased, and immunized. The symptoms were improved. The antibody was injected into the liver, liver, and the liver, and the antibody was injected into the liver, liver and liver. The antibody was injected into the liver, the liver and the liver, and the maximum was 10 months. However, in the current treatment, 17 cases were treated and 1 case was found to be infected with antibodies, antibodies and abortions. IL-6 multi-color physiological function, several kinds of disease disease in service, and the use of bed and bed equipment may be affected. This time, the IL-6 international health care provider and the health care provider confirmed that the disease occurred at the same time, and the IL-6 treatment system was effective in preventing the disease. The new treatment method is effective.