Interleukin-1α

Although the IL-1α molecule has long been recognized, information about its distinct role in various diseases is limited, since most clinical studies have focused on the role of IL-1β. Despite triggering the same IL-1 receptor as does IL-1β, there is, however, a distinct role for IL-1α in some inflammatory diseases. IL-1α is a unique cytokine since it is constitutively present intracellularly in nearly all resting non-hematopoietic cells in health as well as being up-regulated during hypoxia. During cell necrosis, IL-1α functions as an alarm molecule and thus plays a critical role early in inflammation. Following its release from damage tissue cells, IL-1α mediates neutrophil recruitment to the site of injury, inducing IL-1β, other cytokines and chemokines from surrounding resident cells. Another unique attribute of IL-1α is its nuclear localization sequence present in the N-terminal half of the precursor termed the propiece. The IL-1α propiece translocates into the nucleus and participates in the regulation of transcription. Therefore, IL-1α, like IL-1 family members IL-33 and IL-37, is a ‘dual-function’ cytokine binding to chromatin as well as to its cell surface receptor. Some cancer cells can express membrane IL-1α, which can increase immunogenicity of tumor cells and serve in anti-tumor immune surveillance and tumor regression. However, in the tumor microenvironment, precursor IL-1α released from dying tumor cells is inflammatory and, similar to IL-1β, increases tumor invasiveness and angiogenesis.