Swine Interleukin-6 (IL-6) is a multifunctional pro-inflammatory cytokine and a central member of the IL-6 cytokine family—including IL-6, IL-11, IL-27, IL-31, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), and cardiotrophin-like cytokine factor 1 (CLCF1)—which signal through receptor complexes containing the shared gp130 subunit to activate JAK/STAT and MAPK pathways. In pigs (Sus scrofa domesticus), IL-6 is rapidly produced by macrophages, monocytes, endothelial cells, and epithelial cells in response to infection, tissue injury, and stress, where it regulates acute-phase protein synthesis (including C-reactive protein, haptoglobin, and serum amyloid A), fever, leukocyte activation, and B- and T-cell differentiation. Elevated IL-6 levels are associated with economically significant diseases such as porcine reproductive and respiratory syndrome (PRRS), swine influenza, African swine fever, bacterial sepsis, enteric infections, and post-weaning multisystemic wasting syndrome, where dysregulated IL-6 responses can contribute to systemic inflammation and reduced growth performance. As both a biomarker of immune activation and a mediator of disease severity, swine IL-6 is widely used in herd health monitoring, vaccine evaluation, and immunopathogenesis studies. In translational research, pigs serve as valuable large-animal models due to physiological and immunological similarities to humans, and characterization of swine IL-6 and related family members supports studies in infectious disease, sepsis, trauma, metabolic disorders, and immunomodulatory therapeutic development.