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Virtually every organism has evolved mechanisms by which, upon stimulation, lipids are released from plasma membranes and metabolized into mediators capable of changing cellular physiology. As these lipids are present at the first site exposed to external challenge, they provide an ideal substrate for the synthesis of defensive mediators and homeostatic regulators. One such group of lipid mediators is the prostanoids, including the prostaglandins (PGs) and thromboxanes (TXs). Soon after their initial isolation and characterization, the ability of prostanoids to influence inflammation and immune responses was recognized. For example, administration of prostanoids, either alone or in combination, could reproduce the cardinal signs of inflammation. Because they could induce inflammatory changes when injected into tissue and were present at high levels in inflamed lesions, prostanoids were initially categorized as proinflammatory mediators. As our understanding of prostanoid physiology has evolved, it has become clear that these mediators can act to both promote and inhibit inflammation. Thus, it is more accurate to envision these molecules as part of a complex regulatory network that modulates the actions of immune cells and the surrounding microenvironment. Their overall impact in an individual inflammatory response will depend on several factors, including the level of immune cell activation, the presence of other mediators, and the physiological state of the organism. Our ability to dissect the role of prostanoids in complex inflammatory responses has been substantially advanced by the recent development of mouse lines with targeted mutations of genes encoding enzymes and receptors in the prostanoid pathway. In this review we will develop the concept that prostanoids are both effectors and regulators of inflammation, emphasizing new information provided by these mouse models.
Tilley et al. (Sun,) studied this question.