Role of interleukin-1 in bacterial atherogenesis

The high incidence of cardiovascular diseases resulting from atherosclerosis, especially in individuals lacking classic risk factors, has spawned interest in the possibility of unrecognized risk factors, such as chronic bacterial infection. Longstanding low-grade infections, such as periodontal disease, have the potential to affect distant sites in the body by inducing host cells to release inflammatory mediators into the bloodstream. Inflammatory mediators are released by macrophages upon interaction with activated T-helper cells or upon direct recognition of bacterial antigens, and by nonimmune cells upon recognition of antigen through Toll-like receptors. One key mediator, interleukin-1 (IL-1) is released in response to bacterial infection and is known to have specific proatherogenic properties. Increased levels of IL-1 enhance vascular adhesion, vascular permeability, macrophage activation, endothelial and smooth muscle cell proliferation, and protease-induced plaque rupture - all key steps in the progression of atherogenesis. In a recent study, we demonstrated a profound reduction in the progression of atherosclerosis in IL-1 knockout mice. IL-1 holds potential as a target for future antiatherosclerotic therapies, although given its ubiquity in the body, this would not come without unwanted side effects, such as immunosuppression.