Interleukin 11 (IL-11) is a pharmaceutically relevant cytokine. Presently, recombinant IL-11 is used as a treatment for thrombocytopenia, as IL-11 stimulates platelet production. Recently, roles for IL-11 have been identified in several cancers, including breast, colon and gastrointestinal cancer. This suggests that IL-11 signalling inhibition is useful in the treatment of these cancers. IL-11 is an IL-6 family cytokine, and like IL-6, is believed to form a hexameric signalling complex consisting of two copies each of IL-11, an IL-11 specific receptor (IL-11Rα) and the shared signalling receptor gp130.
Our laboratory studies the IL-11 signalling complex using a variety of biophysical methods, including X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy and analytical ultracentrifugation (AUC). We have recently begun NMR studies into IL-11, with the aim of understanding the role of cytokine structural dynamics in complex formation. We have also studied the formation of the IL-11/IL-11Rα complex using AUC. A highly potent IL-11 signalling antagonist has previously been developed, based on a heavily mutated IL-11, the IL-11 mutein (1). We have begun to characterise the IL-11 mutein, and study it’s interaction with the IL-11 receptors. We are undertaking NMR studies into the mutein, aiming to understand any changes in structural dynamics resulting from the mutations. These experiments will result in a structural understanding of IL-11 signalling, and will assist in the development of new therapeutics targeting IL-11 signalling.