Figures & data
Figure 1 The NLRP3 inflammasome is generally assembled upon activation by a range of pathogen-associated molecular patterns through pattern recognition receptors (PRRs) such as TLRs (eg, LPS activation of TLR4), or by interaction with components of internalized damage associated molecular pattern molecules (eg, uric acid crystals) leading to IL-1 cytokine maturation. Mutations to the NACHT domain of the NLRP3 subunit can result in spontaneous activation of the inflammasome and may lead to over-production and secretion of IL-1β, which is thought to be a causative factor in the clinical manifestations of CAPS.
Figure 2 A diagram to illustrate the structural differences of the endogenous IL-1 receptor complex and the designer protein rilonacept. A) Rilonacept – a dimeric protein comprising the IL-1RI chain and IL-1R-ACP chain, linked by fusion to Fc domains which confer an extended half-life. B) Endogenous membrane bound IL-1 receptor complex of IL1-RI and IL-1R-AcP. Both receptor chains are required for IL-1 binding to initiate signal transduction. Rilonacept is able to bind IL-1β with greater affinity.
Table 1 A summary of new clinical trials evaluating rilonacept in other IL-1 related disorders as well as CAPSCitation46