title: 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.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8120, Japan. hanawa@med.niigata-u.ac.jp
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ota
authors.forename: Limin
authors.initials: L
authors.lastname: Ding
authors.forename: He
authors.initials: H
authors.lastname: Chang
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoshida
authors.forename: Keita
authors.initials: K
authors.lastname: Otaki
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hao
authors.forename: Sou
authors.initials: S
authors.lastname: Kasahara
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation; D020128:Inhibitory Concentration 50; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D010957:Plasmids; D011485:Protein Binding; D015202:Protein Engineering; D055503:Protein Multimerization; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D000893:Anti-Inflammatory Agents; D007136:Immunoglobulins; D053577:Interleukin-1 Receptor Accessory Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins