Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, is a pleiotropic cytokine involved in inflammatory responses, tissue remodeling, and immune regulation. It signals through two receptor complexes: the type I receptor (OSMRβ-gp130) and the type II receptor (LIFRβ-gp130), activating downstream pathways like JAK-STAT, MAPK, and PI3K-Akt. OSM is primarily produced by immune cells (e.g., T cells, macrophages) and stromal cells under inflammatory or fibrotic conditions. Dysregulated OSM expression is linked to chronic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease), fibrosis (e.g., lung, liver), and cancer progression, where it promotes cell survival, angiogenesis, and extracellular matrix deposition.
OSM-targeting antibodies have emerged as therapeutic candidates to block its pathogenic signaling. These antibodies inhibit OSM binding to its receptors, suppressing pro-inflammatory and pro-fibrotic cascades. Preclinical studies demonstrate efficacy in reducing inflammation and fibrosis in models of lung, liver, and skin diseases. Challenges include optimizing specificity to avoid interference with beneficial functions of related cytokines (e.g., LIF, IL-6) and managing potential side effects. Current research focuses on humanized monoclonal antibodies and bispecific formats, with early-phase clinical trials exploring their safety and effectiveness in conditions like idiopathic pulmonary fibrosis and autoimmune disorders. OSM antibodies represent a promising strategy for diseases with limited treatment options.