Beyond inflammation: Lipoxins; resolution of inflammation and regulation of fibrosis

It is increasingly apparent that effective host defence involves biphasic production of mediators. An initial acute response involves leukocyte activation and recruitment, a second phase is characterised by the production of mediators regulating phagocytic clearance of apoptotic cells and the active suppression of the initial inflammatory response [ 1 ]–[ 10 ]. Eicosanoid production in inflammation tightly regulates these processes. During the initial phase, proinflammatory mediators including leukotriene (LT) B 4 , the cysteinyl LTs and prostaglandins (PG) evoke potent chemotactic responses of leukocytes whose activation is coupled to the production of proinflammatory (Th1-derived cytokines) at sites of inflammation [ 11 ]. To facilitate resolution, a second phase of lipid mediators may be produced favouring agents with “pro-resolution activities”, including lipoxins (LXs) and the more recently described resolvins and protectins [ 5 , 12 – 20 ]. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.