Inflammation is a protective response essential for maintaining human health and 
for fighting disease. As an active innate immune reaction to challenge, 
inflammation gives rise to clinical cardinal signs: rubor, calor, dolor, tumor 
and functio laesa. Termination of acute inflammation was previously recognized 
as a passive process; a natural decay of pro-inflammatory signals. We now 
understand that the natural resolution of inflammation involves well-integrated, 
active, biochemical programs that return tissues to homeostasis. This review 
focuses on recent advances in the understanding of the role of endogenous lipid 
mediators that modulate cellular fate and inflammation. Biosynthesis of 
eicosanoids and other lipids in exudates coincides with changes in the types of 
inflammatory cells. Resolution of inflammation is initiated by an active class 
switch in lipid mediators, such as classic prostaglandins and leukotrienes, to 
the production of proresolution mediators. Endogenous pro-resolving lipid 
mediators, including arachidonic acid-derived lipoxins, aspirin-triggered 
lipoxins, ω3-eicosapentaenoic acid-derived resolvins of the E-series, 
docosahexaenoic acid-derived resolvins of the D-series, protectins and maresins, 
are biosynthesized during the resolution phase of acute inflammation. Depending 
on the type of injury and the type of tissue, the initial cells that respond are 
polymorphonuclear leukocytes, monocytes/macrophages, epithelial cells or 
endothelial cells. The selective interaction of specific lipid mediators with G 
protein-coupled receptors expressed on innate immune cells (e.g. G 
protein-coupled receptor 32, lipoxin A4 receptor/formyl peptide receptor2, 
chemokine-like receptor 1, leukotriene B4 receptor type 1 and cabannoid receptor 
2) induces cessation of leukocyte infiltration; vascular permeability/edema 
returns to normal with polymorphonuclear neutrophil death (mostly via 
apoptosis), the nonphlogistic infiltration of monocyte/macrophages and the 
removal (by macrophages) of apoptotic polymorphonuclear neutrophils, foreign 
agents (bacteria) and necrotic debris from the site. While an acute inflammatory 
response that is resolved in a timely manner prevents tissue injury, inadequate 
resolution and failure to return tissue to homeostasis results in 
neutrophil-mediated destruction and chronic inflammation. A better understanding 
of the complex mechanisms of lipid agonist mediators, cell targets and actions 
allows us to exploit and develop novel therapeutic strategies to treat human 
inflammatory diseases, including periodontal diseases.