Interleukin-1β (IL-1β) is a proinflammatory cytokine that is implicated in many 
autoinflammatory disorders, but is also important in defense against pathogens. 
Thus, there is a need to safely and effectively modulate IL-1β activity to 
reduce pathology while maintaining function. Gevokizumab is a potent anti-IL-1β 
antibody being developed as a treatment for diseases in which IL-1β has been 
associated with pathogenesis. Previous data indicated that gevokizumab 
negatively modulates IL-1β signaling through an allosteric mechanism. Because 
IL-1β signaling is a complex, dynamic process involving multiple components, it 
is important to understand the kinetics of IL-1β signaling and the impact of 
gevokizumab on this process. In the present study, we measured the impact of 
gevokizumab on the IL-1β system using Schild analysis and surface plasmon 
resonance studies, both of which demonstrated that gevokizumab decreases the 
binding affinity of IL-1β for the IL-1 receptor type I (IL-1RI) signaling 
receptor, but not the IL-1 counter-regulatory decoy receptor (IL-1 receptor type 
II). Gevokizumab inhibits both the binding of IL-1β to IL-1RI and the subsequent 
recruitment of IL-1 accessory protein primarily by reducing the association 
rates of these interactions. Based on this information and recently published 
structural data, we propose that gevokizumab decreases the association rate for 
binding of IL-1β to its receptor by altering the electrostatic surface potential 
of IL-1β, thus reducing the contribution of electrostatic steering to the rapid 
association rate. These data indicate, therefore, that gevokizumab is a unique 
inhibitor of IL-1β signaling that may offer an alternative to current therapies 
for IL-1β-associated autoinflammatory diseases.