Melatonin effect on endothelial cells reduces vascular permeability increase induced by leukotriene B4

The aim of this study was to investigate the effect of melatonin on the inflammatory increase in vascular permeability. Vascular permeability was stimulated by a nonspecific pro-inflammatory agent (carrageenan), by drugs that disrupt endothelial cells junction (histamine, serotonin or bradykinin) or drugs that promote neutrophil recruitment (leukotriene B4 or N-formyl-methionyl-leucyl-phenylalanine fMLP). Vascular permeability was measured by Evan's blue dye extravasation after simultaneous injection of melatonin and the pro-inflammatory drugs in rat dorsal skin. Melatonin only reduced the increase in vascular permeability induced by leukotriene B4, which activates both neutrophil and endothelial cells. The neutrophil expression of CD18 induced by leukotriene B4 or fMLP was not changed by melatonin. On the other hand, melatonin inhibited the leukotriene B4-induced endothelial cells hyperadhesiveness. Our findings suggest that vascular permeability reduction induced by local melatonin injection is mediated by a reduction of endothelial cells ability to interact with neutrophils.