ABSTRACT

This chapter discusses two lipid mediators, leukotriene (LT) B4 and platelet-activating factor (PAF), which are very potent proinflammatory molecules, as potentially powerful immunoregulatory agents. LTB4 is derived from the oxidative metabolism of arachidonic acid. When LTB4 was added to human peripheral blood mononuclear leukocyte cultures stimulated with the mitogenic lectins concanavalin A or phytohemagglutinin, a modest inhibition of the proliferative response could be observed. Many of the effects of LTB4 on lymphocyte functions could be amplified or modulated by interactions of this mediator with accessory cells, such as monocytes. An analogous effect was observed when the production of tumor necrosis factor by human monocytes was assessed in the presence of graded concentrations of LTB4. A factor released by stimulated leukocytes which could activate platelets was described in the late 1960s and early 1970s and termed PAF. Cellular sources of PAF are numerous and include various leukocyte populations and endothelial cells.