The Dual Nature of Oncostatin M: Context-Dependent Mediator of Immunity and Fibrosis.

Oncostatin M (OSM) is a pleiotropic cytokine within the IL-6 family that exhibits dual functions characterized by both pro-inflammatory and regenerative roles. Initially identified for its anti-proliferative effects on melanoma cells, OSM was later recognized as a key driver of chronic inflammation in diseases such as rheumatoid arthritis, inflammatory bowel disease, and pulmonary fibrosis. It activates canonical pathways including JAK/STAT3, MAPK, and PI3K/Akt, as well as regulatory feedback mediated by SOCS3. Recent evidence reveals that OSM sustains pathological cytokine networks via positive feedback loops involving IL-6, TNF-α, and IL-1β, contributing to chronic immune activation and tissue damage. Concurrently, OSM promotes immune suppression by inducing Treg expansion, M2 macrophage polarization, and ECM remodelling, leading to fibrosis and tumour immune evasion. Importantly, OSM-STAT3 signalling antagonizes IFN-γ-STAT1 pathways, impairing protective Th1 immunity in infection and malignancy contexts. Emerging studies underscore OSM’s role in immune endotype switching-shifting inflammatory profiles from Th1/Th17 to immunoregulatory or Th2-like phenotypes-across multiple disease settings including tuberculosis, asthma, chronic infection, cancer, and fibrotic disorders. Conversely, in tissues, OSM exhibits reparative and regenerative functions, mediated largely via the PI3K/Akt axis under a distinct receptor context. This mini-review dissects the molecular architecture underlying OSM’s functional plasticity, explores its contributions to inflammation, fibrogenesis, and evaluates therapeutic targeting strategies-including Oncostatin M receptor blockade and combination pharmacologic approaches. We propose that precision inhibition of OSM signalling may offer novel interventions across a spectrum of chronic inflammatory, fibrotic, and neoplastic diseases, provided that regenerative functions are preserved.