PROLONGED MICROVASCULAR VASODILATION INDUCED BY LEUKOTRIENE B-4 IN HUMAN SKIN IS CYCLOOXYGENASE INDEPENDENT

When the potent chemoattractant leukotriene B-4 (LTB(4)) is applied to pically to human skin it causes delayed onset, long-lasting leukocyte accumulation and erythema. We investigated the role of prostaglandins in the increase in local blood flow by applying LTB(4) topically to th e forearm skin of 22 healthy male volunteers and measuring the effect of the anti-inflammatory compounds tenidap, naproxen and indomethacin. Local microvascular blood flow responses were measured by laser Doppl er flow probe and planimetry. LTB(4) induced dose-dependent increases in blood flow which were maximal at 48 hr and lasted 4 days. Laser Dop pler flow (% flux) at 48 hr was 2.7 +/- 0.1, 20.6 +/- 3.1, 28.7 +/- 2. 4 and 30.2 +/- 2.3% in control and 3, 10, 30 ng/site LTB(4), respectiv ely (mean +/- S.E.M.). In eight subjects the intradermal injection of indomethacin, at a dose (3 X 10(-9) mol/site) that inhibited significa ntly the increased flow induced by intradermally injected arachidonic acid (1 X 10(-9) mol/site, n = 6), had no effect on the increased skin blood flow response induced by LTB(4) (10 ng/site) at 48 hr. Blood fl ow in vehicle-injected LTB(4) sites was 810 +/- 150% above basal and 8 19 +/- 149% in sites injected with indomethacin. In 20 subjects, the e ffect of the anti-inflammatory drugs naproxen and tenidap given orally on the skin blood flow responses to LTB(4) were compared in a double- blind crossover design. The 1085 +/- 98% increase in local blood flow induced by 30 ng of LTB(4) at 48 hr was unaltered at the end of the tr eatment periods with either naproxen or tenidap, where blood flow in t he LTB(4)-treated sites was increased 1018 +/- 131% and 1034 +/- 130%, respectively. Because the vasodilator response to exogenous LTB(4) wa s not altered by nonsteroidal anti-inflammatory drugs either injected locally or taken orally, we suggest that endogenous prostaglandins are not involved in this response.