Thalidomide enhances superoxide anion release from human polymorphonuclear and mononuclear leukocytes.

The effect of thalidomide on the function of human polymorphonuclear leukocytes (PMNs) and blood monocytes was tested in vitro. The chemotactic and spontaneous migration was not affected by thalidomide between 0.001 and 0.1 mg/ml. PMN oxygen consumption was not changed after pre-incubation with thalidomide. However, superoxide anion release upon stimulation of the cells with phorbol-myristate-acetate or the chemotactic tripeptide N-f-Methionyl-Leucyl-Phenylalanine was enhanced in a dose-dependent manner after pre-incubation with thalidomide. Both PMNs and monocytes were influenced. Leukocytes from two patients with chronic granulomatous disease (defective in oxidative burst response) remained unable to produce superoxide anion after pre-incubation with thalidomide. Thus, we suggest that thalidomide primes the phagocytes to respond with an enhanced superoxide anion release upon stimulation. These findings do not explain the anti-inflammatory effect of thalidomide but could have relevance in conditions with quantitative defects in phagocyte oxidative responsiveness.