Dominant soluble modulators of IL-1 molecules
The best characterized of the IL-1 family of cytokines are the agonists, IL-1a and IL-1b, and the receptor antagonist, IL-1Ra. IL-1a and, to a lesser degree, IL-1b bind to the cell signalling receptor, IL-1RI. This recruits another cellular receptor, IL-1 receptor accessory protien (IL-1R AcP) resulting in a high affinity binding and receptor signalling to the cell (left). IL-1Ra also binds to IL-1RI, but it only binds to IL-1RI (and IL-1RII) and NOT to the IL-1R AcP; this does not generate a signal to the cell and it prevents the agonists IL-1a and IL-1b from activating the target cells. Another receptor, IL-1RII, does not signal to the cell(s); it preferentially binds IL-1b.
IL-1RI and IL-1RII also exist in soluble forms. However, the naturally occurring soluble receptors bind differently than the cellular counterparts: sIL-1RI binds preferentially to IL-1Ra and sIL-1RII binds preferentially to IL-1b. None of the natural soluble receptors bind IL-1a, which however binds strongly to natural autoantibody (aAb) to IL-1a.