Regulation of macrophage activation and inflammation by spermine: A new chapter in an old story

Spermine, a naturally occurring polyamine, is a ubiquitous structural compo nent of all eukaryotic cells. Regenerating tissues produce higher levels of spermine, and injured or dying cells release spermine into the extracellul ar milieu, so that tissue levels increase significantly at inflammatory sit es of infection or injury. Recent research has focused on delineating the s ignificance of spermine accumulation in the inflammatory process. The disco very that spermine is a negative regulator of macrophage activation provide d a mechanism by which spermine influences the biology of inflammation. Mec hanistic studies indicate that spermine is incorporated into macrophages an d restrains the innate immune response. This anti-inflammatory process is f acilitated by the negative acute-phase protein, fetuin.