Prostaglandins, leukotrienes, phospholipase, platelet activating factor, and cytokines: an integrated approach to inflammation of human skin.

The purpose of this review is to underline the interactions between eicosanoids, platelet activating factor and IL-1. While the evidence for arachidonate metabolites, especially 12-HETE and the leukotrienes, as major mediators of skin inflammation is persuasive, we wish to draw attention to the potential importance of leukotrienes and prostaglandins as modulators of PAF and IL-1 activity. Phospholipase A2 emerges as a key enzyme in relation to the three above-mentioned mediator classes of human skin. Activation of phospholipase A2 leads to synthesis of both eicosanoids and PAF. Leukotriene products in addition to being pro-inflammatory per se also enhance IL-1 formation whilst cyclo-oxygenase products inhibit IL-1. Prostaglandin E2 also potentiates the actions of PAF. In this scheme it appears improbable that selective inhibition of one component (e.g. a PAF antagonist) or one enzyme (e.g. a 5-lipoxygenase inhibitor) would do more than create an imbalance in this closely integrated network of mediators which might not necessarily be beneficial. On the other hand phospholipase A2 inhibitors including lipocortin would seem to have a greater chance of clinical usefulness because of the central role this enzyme appears to play in the formation or modulation of all these classes of mediator.