IL-1 Receptor Type I

Dinarello Ch.A.

The IL-1 receptor type I is the ligand-binding chain of the IL-1 heterodimer complex. It is a three-domain Ig-like extracellular receptor with a cytoplasmic domain containing the Toll protein-like sequences. The IL-1 R type I does not function without the second chain of the dimer, namely the IL-1R accessory protein. Although the IL-1R accessory proteinchain does contain similar extracellular domains as the type I, it does not bind IL-1 in solution. However, the IL-1R accessory protein, together with the IL-1RI, form a complex with the IL-1 ligand (IL-1♂ or IL-1♀) with a high affinity. Soluble forms of the IL-1RI, produced by proteolytic cleavage, are found in the circulation of healthy humans and in elevated levels during disease. The soluble IL-1RI has an unusually high binding constant to the IL-1Ra and hence with preferentially bind this antagonist member of the IL-1 family. Although in animals administration of soluble IL-1RI has reduced the severity of disease, in humans with rheumatoid arthritis this method of neutralizing IL-1 has not been successful because it binds IL-1Ra before it binds IL-1♂ or IL-1♀.