Interleukin-1 α (IL-1 α) is expressed by epithelial cells, activated macrophages, neutrophils, and endothelial cells to regulate immune responses. IL-1 α signals through the IL-1 receptor, type 1 (IL-1R1) to activate the myeloid differentiation primary response 88 (MYD88) signaling pathway, which contains the cytoplasmic Toll/IL-1 receptor (TIR) domain adapter. IL-1 α and the independently regulated IL-1 β protein have overlapping proinflammatory activities to induce adhesion molecule expression on epithelial cells, control fever induction, initiate rheumatoid arthritis, and promote septic shock.