JPH04169538A - Interleukin-6 acting inhibitor - Google Patents
Interleukin-6 acting inhibitorInfo
- Publication number
- JPH04169538A JPH04169538A JP29566290A JP29566290A JPH04169538A JP H04169538 A JPH04169538 A JP H04169538A JP 29566290 A JP29566290 A JP 29566290A JP 29566290 A JP29566290 A JP 29566290A JP H04169538 A JPH04169538 A JP H04169538A
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- JP
- Japan
- Prior art keywords
- antibody
- receptor
- human
- action
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108090001005 Interleukin-6 Proteins 0.000 title claims abstract description 33
- 229940100601 interleukin-6 Drugs 0.000 title claims abstract description 28
- 239000003112 inhibitor Substances 0.000 title claims abstract description 9
- 102000004889 Interleukin-6 Human genes 0.000 title abstract description 27
- 102000005962 receptors Human genes 0.000 claims abstract description 16
- 108020003175 receptors Proteins 0.000 claims abstract description 16
- 230000009471 action Effects 0.000 claims abstract description 15
- 230000000694 effects Effects 0.000 claims description 6
- 230000016784 immunoglobulin production Effects 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 208000005485 Thrombocytosis Diseases 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 11
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 abstract description 10
- 102000052611 human IL6 Human genes 0.000 abstract description 10
- 210000004027 cell Anatomy 0.000 abstract description 8
- 206010035226 Plasma cell myeloma Diseases 0.000 abstract description 4
- 210000004408 hybridoma Anatomy 0.000 abstract description 4
- 201000000050 myeloid neoplasm Diseases 0.000 abstract description 4
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 238000010353 genetic engineering Methods 0.000 abstract description 3
- 239000000427 antigen Substances 0.000 abstract 1
- 102000036639 antigens Human genes 0.000 abstract 1
- 108091007433 antigens Proteins 0.000 abstract 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 17
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000012895 dilution Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 101001076414 Mus musculus Interleukin-6 Proteins 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 241000700198 Cavia Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000003582 thrombocytopenic effect Effects 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- -1 manntol Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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- 210000004881 tumor cell Anatomy 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は抗ＩＬ−６レセプター抗体を含んで成る、生理
活性物質であるＩ Ｌ−６の作用抑制剤に関するもので
ある。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an agent for inhibiting the action of IL-6, a physiologically active substance, which comprises an anti-IL-6 receptor antibody.
インターロイキン−６（ＩＬ−６）は、免疫、造血、炎
症等の生体防御系において重要な役割を果たしており、
生体の増殖分化に広く関与するタンパク質であるが、一
方ＩＬ−６の生体内での過剰産生は、自己免疫疾患の原
因のひとつとして知られている（岸本、Ｂｌｏｏｄ、７
４．ｐｌ、１９８９年参照）。したがって生体内でＩ
Ｌ−６の作用を人為的に抑制することは、自己免疫疾患
の新しい治療のメカニズムとして期待されている。Interleukin-6 (IL-6) plays an important role in biological defense systems such as immunity, hematopoiesis, and inflammation.
It is a protein that is widely involved in the proliferation and differentiation of living organisms, but on the other hand, overproduction of IL-6 in living organisms is known to be one of the causes of autoimmune diseases (Kishimoto, Blood, 7).
4. pl, 1989). Therefore, in vivo I
Artificially suppressing the action of L-6 is expected to be a new therapeutic mechanism for autoimmune diseases.
しかしながら、Ｉ Ｌ−６の作用を人為的に確実に抑制
する手段はまだ見出されていない。However, no means for artificially and reliably suppressing the effects of IL-6 has yet been found.
（発明が解決しようとする課題〕
従って本発明はｒ Ｌ−６の作用を抑制するための新規
な手段を提供しようとするものである。(Problems to be Solved by the Invention) Therefore, the present invention seeks to provide a novel means for suppressing the action of rL-6.
本発明者は前記の課題を解決すべく種々検討の結果、Ｉ
Ｌ−６レセプターに対する抗体がＩＬ−６の生物学的
作用を抑制するという驚くべき知見を得、これに基いて
本発明を完成した。As a result of various studies to solve the above-mentioned problems, the inventor has found that I
The present invention was completed based on the surprising finding that an antibody against the L-6 receptor suppresses the biological effects of IL-6.
従って本発明は、抗ＩＬ−６レセプターに対する抗体を
含んで成る、Ｉ Ｌ−６作用抑制剤を提供するものであ
る。Therefore, the present invention provides an IL-6 action inhibitor comprising an antibody against anti-IL-6 receptor.
本発明において使用する抗ＩＬ−６レセプター抗体は、
Ｉ Ｌ−６レセプターを特異的に認識するものであり、
これにはモノクローナル抗体及びポリクローナル抗体が
含まれる。本発明における抗体の製造のために用いられ
るヒトＩ Ｌ−６レセプターを含む免疫原としては、ヒ
トミエローマ細胞Ｕ２６６で例示されるヒトＩ Ｌ−６
レセプタ一発現細胞、Ｍｌで例示されるヒトＩＬ−６レ
セブター発現細胞、遺伝子工学的に作製された可溶性ヒ
トＩＬ−６レセブター（特願平１−９７７４参照）等が
挙げられる。The anti-IL-6 receptor antibody used in the present invention is
It specifically recognizes IL-6 receptor,
This includes monoclonal and polyclonal antibodies. The immunogen containing human IL-6 receptor used for the production of antibodies in the present invention includes human IL-6 exemplified by human myeloma cells U266.
Examples include receptor-expressing cells, human IL-6 receptor-expressing cells exemplified by M1, and genetically engineered soluble human IL-6 receptor (see Japanese Patent Application No. 1-9774).
ポリクローナル抗体の製造は、常法に従って、例えば上
記いずれかの免疫原によりマウス、ウサギ、ラット、モ
ルモット等を免疫感作することによって行うことができ
る。Polyclonal antibodies can be produced according to conventional methods, for example, by immunizing mice, rabbits, rats, guinea pigs, etc., with any of the above-mentioned immunogens.
モノクローナル抗体の製造のためのハイブリドーマの作
製も常法に従って行うことができる。例えば上記いずれ
かの免疫原によりマウスやラント等の哺乳類を免疫し、
この動物から肺臓細胞を得、これを樹立されたミエロー
マ細胞と融合せしめる。Hybridomas for producing monoclonal antibodies can also be produced according to conventional methods. For example, immunizing mammals such as mice and runts with any of the above immunogens,
Lung cells are obtained from this animal and fused with established myeloma cells.
次に、生体内でのＩ Ｌ−６作用に対する阻害性を有す
るモノクローナル抗体を産生ずるハイブリドーマをクロ
ーニングする。生体内でのＩ Ｌ−６作用に対する阻害
性の評価法としては、抗マウスＩＬ−６レセブターモノ
クローナル抗体の場合は、本明細書の実施例で提供され
る方法、すなわちマウスに投与されたヒトＩ Ｌ−６の
血小板増多作用に対する阻害性や、マウスに投与された
ヒトＩＬ−６の抗体産生増強効果に対する阻害性が挙げ
られる。また抗ヒトＩ Ｌ、６レセプタ一モノクローナ
ル抗体の場合は、ヌードマウスに移植されたＩ Ｌ−６
依存性ヒト癌細胞の増殖に対する阻害性が挙げられる。Next, a hybridoma that produces a monoclonal antibody that inhibits IL-6 action in vivo is cloned. In the case of an anti-mouse IL-6 receptor monoclonal antibody, the method for evaluating the inhibitory effect on IL-6 action in vivo is the method provided in the Examples of this specification, that is, human Examples include the inhibitory effect on the thrombocytopenic effect of IL-6 and the inhibitory effect on the antibody production enhancing effect of human IL-6 administered to mice. In addition, in the case of anti-human IL-6 receptor monoclonal antibody, IL-6 transplanted into nude mice
The inhibitory effect on the growth of dependent human cancer cells can be mentioned.
多数のクローンをスクリーニングする際は、まずインビ
トロでのＩＬ−６作用に対する阻害性を評価して、一定
数のクローンを選抜しても良い。When screening a large number of clones, a certain number of clones may be selected by first evaluating their ability to inhibit IL-6 action in vitro.
上記ポリクローナル抗体、及びモノクローナル抗体の回
収・精製方法は、いずれもそれ自体当業界によりよく知
られている方法により行うことができる。The methods for collecting and purifying the polyclonal antibodies and monoclonal antibodies described above can all be performed by methods well known in the art.
本発明中の抗体は、上記方法で調製された天然型の抗体
だけでなく、さらに上記抗体を出発材料として、遺伝子
工学的手法や蛋白化学的方法を用いて作製された人工型
の抗体でもよい。前者の例としては、マウス由来抗ヒト
Ｉ Ｌ−６レセプター・モノクローナル抗体の可変領域
（Ｖ ＳＪ域）とヒト抗体の不変領域（Ｃ領域）を遺伝
子工学的手法で結合させたキメラ型抗体を挙げることが
できる。The antibodies of the present invention may be not only natural antibodies prepared by the above method, but also artificial antibodies produced using genetic engineering methods or protein chemical methods using the above antibodies as starting materials. . An example of the former is a chimeric antibody in which the variable region (VSJ region) of a mouse-derived anti-human IL-6 receptor monoclonal antibody and the constant region (C region) of a human antibody are combined using genetic engineering techniques. be able to.
このような抗体の作製方法は、それ自体当業界によりよ
く知られている方法により行うことができる。また後者
の例としては、パパインで抗体分子を切断し調製されう
るＦａｂｅＪ［域等が挙げられる。Methods for producing such antibodies can be carried out by methods well known per se in the art. Examples of the latter include FabeJ [region], which can be prepared by cleaving an antibody molecule with papain.
なお、ヒトＩ Ｌ−６レセプターに対するモノクローナ
ル抗体は特願平２−１８９４２０号明細書中に、ＰＭＩ
抗体、及びＭ７１Ｂ抗体として記載されており、これら
を本発明において使用することができる。また、マウス
ＩＬ−６レセプターに対する抗体は特願平２−２１５８
８６号明細書に記載されたマウスＩＬ−６レセプターを
免疫原として、常法に従って調製したものを本発明にお
いて用いることができる。The monoclonal antibody against human IL-6 receptor is described in Japanese Patent Application No. 189420/1999 as PMI.
antibody, and M71B antibody, which can be used in the present invention. In addition, antibodies against mouse IL-6 receptor are available from Japanese Patent Application No. 2-2158.
An immunogen prepared using the murine IL-6 receptor described in No. 86 can be used in the present invention by a conventional method.
Ｉ Ｌ−６は細胞膜上のＩ Ｌ−６レセプターと結合し
、さらにｇｆ）１３０に会合し、シグナルが伝達される
。この様なＩＬ−６シグナル伝達経路の過程において、
抗ＩＬ−６レセプター抗体は、生体内でのＩＬ−６作用
を抑制する効果を有する。本発明の抑制剤により抑制さ
れるＩ Ｌ−６の作用としては、血小板増多作用、抗体
産生増強作用、急性期蛋白誘導作用、腫瘍細胞増殖作用
、神経細胞分化作用等が挙げられる。従って、これらの
作用に起因する疾患、例えばミエローマ、慢性関節リウ
マチ、カボジ肉腫、キャッスルマン症候群等の治療にお
いて本発明の抑制剤は有効であると考えられる。IL-6 binds to the IL-6 receptor on the cell membrane, and further associates with gf)130, and a signal is transmitted. In the process of such IL-6 signal transduction pathway,
Anti-IL-6 receptor antibodies have the effect of suppressing IL-6 action in vivo. The effects of IL-6 that are inhibited by the inhibitor of the present invention include thrombocytosis, antibody production enhancement, acute phase protein induction, tumor cell proliferation, nerve cell differentiation, and the like. Therefore, the inhibitor of the present invention is considered to be effective in treating diseases caused by these effects, such as myeloma, rheumatoid arthritis, Kaboji's sarcoma, and Castleman syndrome.
本発明の抑制剤は、好ましくは非経口投与により、例え
ば静脈内投与、筋肉内投与、経皮投与等により投与する
ことができる。投与量は疾患の種類、患者の状態等によ
り異るが、一般にｌＯ■／ｋｇ〜１０ｍｇ／ｋｇの範囲
である。本発明の抗体は常用の賦形剤、例えば生理食塩
水、ブドウ糖液、マンントール、メチルセルロース、ゼ
ラチン等と混合することにより製剤化される。零荊はま
た、凍結乾燥品であることができ、これは使用直前に生
理食塩水、５％ブドウ糖液、リンゲル液等の等張液によ
り再溶解することができる。またつけ加えるならば、ヒ
トに対しては、ヒトＩ Ｌ−６レセプターを免疫原とし
てマウス、ラット等を用いて調製した抗ヒトＩ Ｌ−６
レセプタ一抗体をキメラ化した、ヒト人体において異物
として認識され難いキメラ抗体を用いると良い。The inhibitor of the present invention can be administered parenterally, for example, intravenously, intramuscularly, transdermally, etc. The dosage varies depending on the type of disease, patient's condition, etc., but is generally in the range of 1O2/kg to 10mg/kg. The antibodies of the present invention are formulated by mixing with conventional excipients such as physiological saline, glucose solution, manntol, methylcellulose, gelatin, and the like. Zero Jing can also be a lyophilized product, which can be reconstituted with an isotonic solution such as saline, 5% dextrose, Ringer's solution, etc. immediately before use. In addition, for humans, anti-human IL-6 prepared using human IL-6 receptor as an immunogen in mice, rats, etc.
It is preferable to use a chimeric antibody obtained by chimerizing a receptor-antibody and which is difficult to be recognized as a foreign substance in the human body.
以下本発明をさらに詳細に説明するために実施例を記載
するが、本発明はこれら実施例により限定されるもので
はない。Examples will be described below to explain the present invention in more detail, but the present invention is not limited by these Examples.
ｚ巖桝よ、 マウスＩ Ｌ−６レセプター・ポリク抗マ
ウスＩＬ−６レセプター・ポリクローナル抗体は、ＣＨ
○細胞由来可溶性マウスＩ Ｌ−６レセプター（特願平
１−２９２２３０号１特願平２−２１５８８６号参照）
をモルモットに免疫して調製した。ＩＣＲマウス（雄性
、５週齢）１群５匹、全４群を用い、その内の一群を未
投与群（対照）とし、他の３群をそれぞれ、■９０鱈の
大腸菌由来りコンビナンドＩＬ−６を１日１回腹腔打ち
に投与する群、０１８１回、９００ｄの抗マウスＩ Ｌ
−６レセプター・ポリクローナル抗体を腹腔内に投与し
た後、９０■の前記リコンビナントＩ Ｌ−６を投与す
る群、■９００ ｔｒｇの抗マウスＩＬ−６レセプター
・ポリクローナル抗体と９０鱈のりコンビナンドＩＬ−
６を混合して１日１回投与する群とし、それぞれ５日間
連続投与した。６日目に後大動脈より全採血し、血小板
数をヘモサイトメーターＰＣ−６０１（エルマ社製）で
計数した。この結果を第１図に示す。Dear Mr. Mouse IL-6 Receptor Polyclonal Anti-Mouse IL-6 Receptor Polyclonal Antibody
○Cell-derived soluble mouse IL-6 receptor (see Japanese Patent Application No. 1-292230 1 Japanese Patent Application No. 2-215886)
was prepared by immunizing guinea pigs. A total of 4 groups of ICR mice (male, 5 weeks old), 5 mice per group, were used, one of which was treated as an untreated group (control), and the other 3 groups were treated with 90 cod E. coli-derived combinant IL- 6 administered by intraperitoneal injection once a day, 0181 times, 900d anti-mouse IL
-6 receptor polyclonal antibody was administered intraperitoneally, followed by 90 μg of the above recombinant IL-6;
6 were mixed and administered once a day, and each was administered continuously for 5 days. On the 6th day, all blood was collected from the posterior aorta, and the number of platelets was counted using a hemocytometer PC-601 (manufactured by Elma). The results are shown in FIG.
第２図から明らかなように、９０鱈／日のＩＬ−６を投
与した群では有意に血小板数が増加しているのに対し、
９００ｘ／日の抗体を投与した群（前記■、■の群）で
は、いずれもＩＬ−６を投与したにもかかわらすＩ Ｌ
−６未投与群（対照）と同じレベル又はそれ以外であっ
た。このことから、抗マウスＩＬ−６レセブター・ポリ
クローナル抗体は、ｉｎ ｖｉｖｏでのＩＬ−６の血小
板増多効果に対する抑制効果を示すことが観察された。As is clear from Figure 2, the number of platelets increased significantly in the group receiving IL-6 at 90 cod/day;
In the groups to which the antibody was administered at 900x/day (groups ① and ② above), despite the administration of IL-6, IL
-6 was at the same level as the non-administered group (control) or other than that. From this, it was observed that the anti-mouse IL-6 receptor polyclonal antibody exhibited an inhibitory effect on the thrombocytopenic effect of IL-6 in vivo.
ＢＡＬＢ／Ｃ７ウス（雄性、５週齢）に、１ ｍｇのＤ
ＮＰ／ＢＳＡ （シグマ社）を皮下投与し、翌日から１
日１回０〜１０バのＩ Ｌ−６及び０〜１００μｇの抗
マウスＩＬ−６レセプター・ポリクローナル抗体（実施
例１参照）の混合液を腹腔内に６日間連続投与した。７
日目に全採血を行い、血清分離をし、抗ＤＮＰ／ＢＳＡ
抗体価を通常のＥＬＩＳＡ法で測定した。BALB/C7 mice (male, 5 weeks old) were given 1 mg of D.
NP/BSA (Sigma) was administered subcutaneously, and from the next day
A mixture of 0 to 10 μg of IL-6 and 0 to 100 μg of anti-mouse IL-6 receptor polyclonal antibody (see Example 1) was administered intraperitoneally once a day for 6 consecutive days. 7
On the day, whole blood was collected, serum was separated, and anti-DNP/BSA
Antibody titers were measured using a conventional ELISA method.
即ち各血清に対し１０倍稀釈を最高濃度とし、さらに２
倍稀釈列を作り、これらの抗ＤＮＰ／ＢＳＡに特異的な
ｒｇｃ量を測定した。That is, for each serum, a 10-fold dilution is the highest concentration, and a further 2
A series of double dilutions was prepared, and the amount of rgc specific to these anti-DNP/BSA was measured.
第２図は横軸にその稀釈倍数を、縦軸にＩｇＧ量に相関
した４０５ｄｍでの吸光度を示したもので、この図から
明らかなように、１０題／日の１ ＞６投与により増加
した抗ＤＮＰ／ＢＳＡ抗体価は、投与した抗体量に依存
して下がり、特に１００ｘ／日の抗体投与では、Ｉ Ｌ
−６未投与のレベル以下に下がった。このように、抗マ
ウスＩＬ−６レセプター・ポリクローナル抗体の、ｉｎ
ｖｉｖｏでのＩＬ−６の抗体産生増強効果に対する抑
制効果が観察された。Figure 2 shows the dilution factor on the horizontal axis and the absorbance at 405 dm correlated with the amount of IgG on the vertical axis. The anti-DNP/BSA antibody titer decreases depending on the amount of antibody administered, and especially when the antibody is administered at 100x/day, I L
-6 It fell below the level of non-administration. In this way, anti-mouse IL-6 receptor polyclonal antibody
A suppressive effect on the antibody production enhancing effect of IL-6 in vivo was observed.
第１図は、Ｉ Ｌ−６及び抗マウスＩ Ｌ−６レセプタ
ー・ポリクローナル抗体を投与されたＩＣＲマウスの血
小板数を示す。
第２図は、ＩＬ−６及び抗マウスＩ Ｌ−６レセプター
・ポリクローナル抗体を投与されたＤＮＰ／ＢＳＡ感作
マウスの抗ＤＮＰ／ＢＳＡ抗体価を示す。
（ｘ ＩＱ’／ＰＬ）
群
＃１：サンプル未投与群
＃２：ｒＬ−６９０μｇ腹腔投与群
＃３：抗マウスＩＬ−６レセブター・ポリクローナル抗
体９００μｇ静脈投与ＩＬ−６９０μｇ腹腔投与群
○Ｄ４０５
血清希釈倍率
２ ＋０ １０
０３１０１０ ＋００FIG. 1 shows platelet counts in ICR mice administered IL-6 and anti-mouse IL-6 receptor polyclonal antibody. FIG. 2 shows anti-DNP/BSA antibody titers in DNP/BSA-sensitized mice administered with IL-6 and anti-mouse IL-6 receptor polyclonal antibody. (x IQ'/PL) Group #1: Sample not administered Group #2: rL-690 μg intraperitoneal administration group #3: Anti-mouse IL-6 receptor polyclonal antibody 900 μg intravenous administration IL-690 μg intraperitoneal administration group ○D405 Serum dilution factor 2 +0 10
031010 +00
Claims (1)
体を含んで成るＩＬ−６作用抑制剤。 ２、ＩＬ−６による血小板増多作用を抑制する、請求項
１に記載のＩＬ−６作用抑制剤。３、ＩＬ−６による抗
体産生増強効果を抑制する、請求項１に記載のＩＬ−６
作用抑制剤。[Claims] 1. An IL-6 action inhibitor comprising an anti-interleukin-6 (IL-6) receptor antibody. 2. The IL-6 action inhibitor according to claim 1, which inhibits the thrombocytosis action caused by IL-6. 3. IL-6 according to claim 1, which suppresses the effect of enhancing antibody production by IL-6.
Action inhibitor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29566290A JPH04169538A (en) | 1990-11-01 | 1990-11-01 | Interleukin-6 acting inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29566290A JPH04169538A (en) | 1990-11-01 | 1990-11-01 | Interleukin-6 acting inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04169538A true JPH04169538A (en) | 1992-06-17 |
Family
ID=17823554
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29566290A Pending JPH04169538A (en) | 1990-11-01 | 1990-11-01 | Interleukin-6 acting inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04169538A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9017677B2 (en) | 1997-03-21 | 2015-04-28 | Chugai Seiyaku Kabushiki Kaisha | Methods of treating a disease mediated by sensitized T cells |
-
1990
- 1990-11-01 JP JP29566290A patent/JPH04169538A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9017677B2 (en) | 1997-03-21 | 2015-04-28 | Chugai Seiyaku Kabushiki Kaisha | Methods of treating a disease mediated by sensitized T cells |
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