Nonsteroidal Antiinflammatory Drugs Induce UV-Dependent Histamine and Leukotriene Release from Peripheral Human Leukocytes

Abstract

The effect of UV-A radiation on the in vitro release of vasoactive mediators from human peripheral leukocytes incubated with different nonsteroidal antiinflammatory drugs (NSAIDs) was studied in the newly developed photo basophil histamine release test (PBHRT). Washed peripheral leukocytes were incubated with 10(-6) to 10(-3) M of various NSAIDs and exposed to 1-100 J/cm2 UV-A. Maximum histamine release was 4% with acetylsalicylic acid, 10% with benoxaprofen, 20% with thiophene, 28% with diclofenac, 39% with tiaprofenic acid, 40% with carprofen, 55% with ketoprofen and not demonstrable with indoprofen. Maximal reactions occurred at UV-A doses of 25 or 50 J/cm2. Leukotriene B4 (LTB4) generation in the supernatants of cells treated with UV-A or NSAID alone was below or close to the detection limit (145 pg/ml). On the contrary, UV-A irradiation of cells incubated with NSAID led to marked LTB4 generation (up to 1,000 pg/ml). The results indicate that many NSAIDs can induce photosensitization in vitro, the PBHRT being a promising new method for identification of possibly phototoxic compounds. Release of vasoactive mediators like histamine or leukotrienes may be involved in the in vivo development of phototoxic or photoallergic side reactions.