IL-1 family cytokines in cardiovascular disease

The interleukin (IL)-1 family is a group of cytokines crucially involved in regulating immune responses to infectious challenges and sterile insults. The family consists of the eponymous pair IL-1 alpha and IL-1 beta, IL-18, IL-33, IL-37, IL-38, and several isoforms of IL-36. In addition, two endogenous inhibitors of functional receptor binding, IL-1R antagonist (IL-1Ra) and IL-36Ra complete the family. To gain biological activity IL-1 beta and IL-18 require processing by the protease caspase-1 which is associated with the multi-protein complex inflammasome. Numerous clinical association studies and experimental approaches have implicated members of the IL-1 family, their receptors, or component of the processing machinery in underlying processes of cardiovascular diseases (CVDs). Here we summarize the current state of knowledge regarding the pro-inflammatory and disease-modulating role of the IL-1 family in atherosclerosis, myocardial infarction, aneurysm, stroke, and other CVDs. We discuss clinical evidence, experimental approaches and lastly lend a perspective on currently developing therapeutic strategies involving the IL-1 family in CVD.