Abstract

At concentrations of 10 micrograms/ml and greater, dithranol (anthralin) caused an intense, dose-related activation of luminol-enhanced chemiluminescence (LECL) of human neutrophils and also increased oxygen consumption by these cells. Activation of LECL, which was maximal with 40 micrograms/ml dithranol, occurred promptly, peaked at 3-5 min, then declined. Dithranol-mediated stimulation of LECL was inhibited by catalase and by the protein kinase C inhibitor, H-7. Neutrophils from individuals with chronic granulomatous disease were unresponsive to the pro-oxidative effects of dithranol. At concentrations of 2.5 micrograms/ml and less, dithranol did not directly activate the LECL responses of neutrophils. However pre-treatment of neutrophils with dithranol at concentrations of 0.5-2.5 micrograms/ml increased the LECL-responses of cells subsequently stimulated with calcium ionophore and opsonized zymosan. These observations demonstrate two distinct dose-related, pro-oxidative interactions of dithranol with human neutrophils: low-dose priming and high-dose activation of oxidant generation. Since phagocyte-derived reactive oxidants are immunosuppressive, these pro-oxidative interactions of dithranol with human neutrophils may contribute to the pharmacotherapeutic mechanisms of this agent.