Swine Interleukin-1 Alpha (IL-1α) is a pro-inflammatory cytokine belonging to the IL-1 family—which includes IL-1α, IL-1β, and the IL-1 receptor antagonist (IL-1Ra)—and plays a central role in initiating innate and sterile inflammatory responses in pigs (Sus scrofa domesticus). IL-1α is constitutively expressed in epithelial and barrier tissues and functions as an intracellular alarmin that is rapidly released upon cell injury, necrosis, or viral infection, triggering early inflammatory signaling independent of inflammasome processing. Upon binding to the IL-1 receptor type 1 (IL-1R1), swine IL-1α activates NF-κB and MAPK pathways that promote leukocyte recruitment, endothelial activation, fever, and amplification of pro-inflammatory cytokine cascades. In swine health, IL-1α is particularly relevant in respiratory and enteric diseases such as porcine reproductive and respiratory syndrome (PRRS), swine influenza, African swine fever, bacterial pneumonia, and intestinal infections, where epithelial damage leads to early IL-1α release and contributes to lung or gut inflammation. While essential for pathogen defense and tissue repair, excessive IL-1α signaling can exacerbate tissue injury and impair growth performance. As an early mediator of sterile and infectious inflammation, swine IL-1α serves as a biomarker of tissue damage and innate immune activation. In translational research, pigs are valuable large-animal models due to physiological similarities to humans, and characterization of swine IL-1α supports studies of cytokine-driven inflammation, sepsis, trauma, and development of targeted IL-1–modulating therapies relevant to both veterinary and human medicine.