Interleukins are a group of cytokines, a secreted proteins and signaling molecules. The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency. The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T and B lymphocytes, and hematopoietic cells.
Interleukin (IL)23, composed of a p19 and a p40 subunit, is suggested to play key roles in rheumatoid arthritis (RA), dependent on the promotion and proliferation of IL17-producing T helper (Th)17 cells. The receptor for this cytokine is heterodimeric and uses a novel second subunit, IL-23R, which is a member of the hematopoietin receptor family. IL-23 sharing a p40 subunit with IL-12 but having a distinct p19 subunit. And IL-23 binds to IL-12Rβ1 but not IL-12Rβ2. IL-23 plays a role in type 1-polarized T cell immune responses. Although IL-12 strongly activates naive T cells, the initial description of IL-23 reported preferential actions on memory T cells to increase IFN-γ production and proliferation. More recent data indicate that IL-23 is a key cytokine controlling inflammation in peripheral tissues. In transgenic mice, overexpression of p19 produces inflammation in multiple organs and epithelial tissues, including the skin.
Mirikizumab, a humanized IgG4 anti-human IL-23p19 monoclonal antibody
Mirikizumab selectively targets the p19 subunit of IL-23 and inhibits the IL-23 pathway. Therefore, Mirikizumab shows efficacy in moderately to severely active ulcerative colitis (UC). Inflammation due to over-activation of the IL-23 pathway plays a critical role in the pathogenesis of UC and Crohn’s disease. Crohn’s disease is a form of inflammatory bowel disease (IBD) that can cause systemic inflammation manifested as abdominal pain, diarrhea, fever and weight loss. It can lead to intestinal obstruction, fibrosis and other complications.
All in all, Mirikizumab (LY3074828) is a humanized IgG4 monoclonal antibody targets the p19 subunit of interleukin 23 that has potential for the research of ulcerative colitis.