New endogenous anti-inflammatory and proresolving lipid mediators: implications for rheumatic diseases

Prostaglandins and leukotrienes are lipid mediators that carry out pivotal roles in host defense and acute inflammation. Failure to completely resolve an acute inflammatory response can lead to chronic inflammation, scarring, and eventual loss of tissue function. Until recently, it was thought that tissue resolution of acute inflammation was a passive event. However, it is now known than lipoxins, which--like prostaglandins and leukotrienes--are also derived from arachidonic acid, are active anti-inflammatory and proresolution mediators, acting in part by reducing neutrophil entry to the inflammation site and stimulating the uptake of apoptotic polymorphonuclear leukocytes by macrophages. Novel families of locally acting and locally generated mediators derived from omega-3 polyunsaturated fatty acids have also been identified as biosynthetically active components in the resolution phase of inflammation. The new families of chemical mediators are termed 'resolvins' and 'protectins' because individual members of each family are stereospecific in controlling the duration and magnitude of inflammation in animal models. Possible deficiencies in the biosynthesis of lipoxins, resolvins, and protectins, and/or their signal transduction, might underlie some aspects of pathogenesis in chronic inflammatory diseases.