15-Hydroxyeicosatetraenoic acid (15-HETE) specifically inhibits the LTB₄-induced skin response

Summary

15-Hydroxyeicosatetraenoic acid (15-HETE), a 15-lipoxygenase product of arachidonic acid, inhibits leukotriene B₄ (LTB₄)-induced chemotaxis of polymorphonuclear leukocytes (PMNs) in vitro. In this study the effects of intradermal injections of LTB₄ were determined in the absence or presence of 15-HETE. For comparison intradermal injections of purified human complement split product C5a were performed in the absence or presence of 15-HETE. The skin response was evaluated by measuring the diameter of the wheal, the area of the flare and by intensity of the erythema (erythema index). LTB₄ and C5a were injected at the concentration of 200 ng/ml. At this concentration the maximal skin response of LTB₄ and C5a were equivalent. In contrast to C5a reaction, which resolved within 1 h, LTB₄-induced skin response lasted up to 18 h. In all subjects the skin response was significantly decreased when LTB₄ was injected together with 300 ng of 15-HETE. The decrease of wheal, flare, and erythema index averaged 81.9%, 56.6%, 53.6%, respectively, when all parameters were obtained at the maximal skin response. In contrast, the C5a-induced skin response was not affected by addition of 15-HETE, even when the final dose of 15-HETE was increased 10 times to 3 μg. The LTB₄-induced reaction could last up to 18 h after injection. After the addition of 300 ng of 15-HETE the skin response resolved after 1 h. The present results demonstrate that 15-HETE is a specific inhibitor of the LTB₄-induced skin response and brings additional evidence in support of the ability of 15-HETE to regulate the proinflammatory effects of LTB₄ in vivo.