The Inhibition of Polymorphonuclear Leukocyte Cytotoxicity by Dapsone: A POSSIBLE MECHANISM IN THE TREATMENT OF DERMATITIS HERPETIFORMIS
AUTOR(ES)
Stendahl, O.
RESUMO
The effect of the sulfone compound 4,4′-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 μg/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H2O2-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaI. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the 51Cr release from virus-induced lymphoma cells. Because the MPO-H2O2-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=371756Documentos Relacionados
- Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment
- The small intestine in dermatitis herpetiformis
- Inhibition of human polymorphonuclear leukocyte chemotaxis by oxygenated sterol compounds.
- DERMATITIS HERPETIFORMIS, THE CELIAC DISEASE OF THE SKIN!
- Dermatitis herpetiformis in an adolescent patient