Local Effects of Synthetic Leukotrienes (LTC4, LTD4, and LTB4) in Human Skin

The local effects of intracutaneous injections into humans of 1–3 mans of five products of arachidonic acid metabolism, leukotrienes (LT) C 4 , D 4 , E 4 , and 8 4 from the 5-lipoxygenase pathways and prostaglandin (PG) D 2 from the cyclooxygenase pathway, were assessed clinically and histologically. In equimolar concentrations, LTC 4 , LTD 4 , and LTE 4 elicited erythema and wheal formation, in which a wheal with central pallor was present up to 2 hr, and the erythema persisted as long as 6 hr. PGD 2 elicited a wheal that lasted up to 1 hr and erythema that lasted up to 2 hr. The dermal vascular sites affected by LTD 4 and PGD 2 included capillaries, superficial and deep venules, and arterioles, LTB 4 elicited a transient wheal and flare, followed in 3–4 hr by induration that was characterized by a dermal infiltrate comprised predominantly of neutrophils. The combination of LTB 4 and PGD 2 elicited tenderness and increased induration associated with a more intense neutrophil infiltration. Thus, the products of the 5-lipoxygenase pathway of arachidonic acid metabolism in nanomole amounts can induce cutaneous vasodilation with edema formation and a neutrophil infiltrate, and these responses are enhanced by a cyclooxygenase pathway product, PGD 2 .