Figure 1. Lipid mediators in the acute inflammatory response, resolution and other outcomes.

LM play pivotal roles in the vascular response and leukocyte trafficking, from initiation to resolution. Eicosanoids are critical in initiating the cardinal signs of inflammation (upper left). The lipoxins, resolvins, protectins and maresins, specialized proresolving mediators (SPM), are produced in self-limited responses (Fig. 2). SPM stimulate cellular events that counter-regulate pro-inflammatory mediators and regulate PMN, monocyte and macrophage response, leading to resolution. Depicted are some pro-resolving actions in leukocyte trafficking (neutrophil-monocyte sequence), lipid mediator class switching and efferocytosis of apoptotic PMN that must occur in resolving exudates for restoration of normal structure and homeostasis. In addition to the release of n-3 substrate from phospholipid stores⁹⁵, omega-3 substrates can enter mouse exudates via edema from peripheral blood⁵⁷. SPM enhance efferocytosis, stimulate signs of resolution (lower right) and signal to adaptive immunity via lymphocytes. Failed resolution may lead to enhanced prostaglandins and leukotrienes, chronic inflammation and fibrosis. SPM counterregulate pro-inflammatory chemical mediators, reducing magnitude and duration of inflammation, and stimulate reepithelialization, wound healing, and tissue regeneration in model organisms.