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01.06.2011

IL-1 Receptor Accessory Protein-Ig/IL-1 Receptor Type II-Ig Heterodimer Inhibits IL-1 Response More Strongly than Other IL-1 Blocking Biopharmaceutical Agents

verfasst von: Haruo Hanawa, Yoshimi Ota, Limin Ding, He Chang, Kaori Yoshida, Keita Otaki, Kazuhisa Hao, Sou Kasahara, Makoto Kodama, Mikio Nakazawa, Yoshifusa Aizawa

Erschienen in: Journal of Clinical Immunology | Ausgabe 3/2011

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Abstract

Introduction

Interleukin (IL)-1 is a key orchestrator of inflammation and IL-1 inhibitors are expected to be promising pharmaceutical agents for such pathologies. IL-1 is bound to the complex of two receptor components with much higher affinity than with either receptor component alone.

Materials and Methods

We examined the effect of a heterodimer of IL-1 receptor accessory protein (Acp)-immunoglobulin (Ig) and IL-1R type II (IL1R2)-Ig named AcP-Ig/IL1R2-Ig heterodimer, and compared its effects with other IL-1 inhibitors reported previously.

Results and Discussion

Our results demonstrated that the rat AcP-Ig/IL1R2-Ig heterodimer (IC50 = 1.95 pM) inhibited IL-1 response to a greater extent than IL1RA (IC50 = 1,935 pM), Acp-IL1R type I (IL1R1)-Ig homodimer (IC50 = 73.7 pM) and Acp-IL1R2-Ig homodimer (IC50 = 72.8 pM). Moreover, human AcP-Ig/IL1R2-Ig heterodimer (IC50 = 0.14 pM) inhibited it to a greater extent than Acp-IL1R1-Ig homodimer (IC50 = 4.48 pM) and strongly inhibited responses of both IL-1α and IL-1β.

Conclusions

The AcP-Ig/IL1R2-Ig heterodimer, which is similar to the original extracellular structure of the Acp/IL1R1 complex, may inhibit the IL-1 response more vigorously than other IL-1 blocking biopharmaceutical agents.

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Titel: IL-1 Receptor Accessory Protein-Ig/IL-1 Receptor Type II-Ig Heterodimer Inhibits IL-1 Response More Strongly than Other IL-1 Blocking Biopharmaceutical Agents
verfasst von: Haruo Hanawa
Yoshimi Ota
Limin Ding
He Chang
Kaori Yoshida
Keita Otaki
Kazuhisa Hao
Sou Kasahara
Makoto Kodama
Mikio Nakazawa
Yoshifusa Aizawa
Publikationsdatum: 01.06.2011
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 3/2011
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-010-9497-z

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Abstract

Introduction

Materials and Methods

Results and Discussion

Conclusions

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