TPA, tetradecanoyl phorbol acetate. immediately in acute inflammation prior to the recruitment of leukocytes. As immune cells infiltrate the tissues, further increases in prostanoid levels are observed. The profile of prostanoids that are produced can also vary dramatically during the course of the response. For example, in the carrageenan-induced pleurisy model, elevated PGE2 levels are observed only during the early stages of inflammation, whereas PGD2 becomes pronounced during the final stages of the response (1).

Prostanoid production depends on the activity of the two COX isoenzymes within cells. COX-1 is present in most cells and its expression is generally constitutive. In contrast, COX-2 expression is low or undetectable in most cells but its expression increases dramatically upon stimulation, particularly in cells of the immune system (2). The recruitment of leukocytes and the induction of COX-2 expression by inflammatory stimuli likely account for the high levels of prostanoids found in chronic inflammatory lesions and provided a rational basis for the development of COX-2–specific inhibitors for treating arthritis and other chronic inflammatory diseases. However, the capacity for COX-1 to modulate inflammatory responses should not be overlooked. Studies of circulating monocytes after exposure to LPS suggest that some increases in COX-1 expression can occur upon activation (3). In addition, studies using mice deficient in the expression of COX-1 or COX-2 have identified unique roles for COX-1 in the initiation of certain inflammatory responses (Table 1). In mast cells, Reddy and associates found that the production of PGD2 within the first 30 minutes of stimulation depends almost entirely on COX-1. While COX-1 also contributes to the production of PGD2 by