Abstract
The resolution phase of inflammation was previously considered to be a passive process. However, recent findings indicate that the resolution of inflammation tends toward being an active process that enables inflamed tissues to return to a state of homeostasis. This process is facilitated by pro-resolving lipid mediators, which are mainly derived from ω6-polyunsaturated fatty acids (PUFA), such as arachidonic acid and ω3-PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The bioactive pro-resolving lipid molecules are 1) lipotoxin A and B, derived from arachidonic acids; 2) resolvin D1-D4, derived from DHA; 3) resolvin E1 and E2, derived from EPA; and 4) protectin D1, derived from DHA. The resolution of inflammation requires pro-resolving mediator-activated programs that stop neutrophil infiltration to inflamed tissues, promote the uptake and clearance of apoptotic inflammatory cells, and stimulate the antimicrobial activities of mucosal epithelial cells. Acetylsalicylic acid (aspirin) promotes the pro-resolving process by facilitating the production of lipoxin, resolvin, and protectin through the acetylation of cyclooxygenase (COX)-2, while selective COX-2 inhibitors block the production of prostaglandins as well as that of pro-resolving molecules. These findings suggest new possibilities in the development of novel prophylactics, nutritional approaches and pharmaceutical therapeutics for the treatment of inflammatory diseases in critical care.
