Clofazimine-mediated enhancement of reactive oxidant production by human phagocytes as a possible therapeutic mechanism.
Clofazimine, at concentrations within the therapeutic range (0.01-5 micrograms/ml), stimulated human polymorphonuclear leucocytes (PMNL) to generate increased amounts of reactive oxidants (RO) when activated with the tripeptide leucoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), calcium ionophore, phorbol myristate acetate and opsonised zymosan. Clofazimine per se did not activate the membrane-associated oxidative metabolism of PMNL, but rather primed these cells to hyperreact to the various stimuli. To investigate the therapeutic significance of these observations clofazimine was administered to patients with various chronic inflammatory diseases (lichen planus, discoid lupus erythematosus and rheumatoid arthritis) and generation of RO by FMLP-activated phagocytes was measured before and during clofazimine administration. A statistically significant potentiation of RO generation by FMLP-activated phagocytes was observed during clofazimine administration. Since RO are immunosuppressive and antimicrobial the therapeutic mechanisms of clofazimine may be related to pro-oxidative interactions of this agent with phagocytes.
Anderson
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R
Department of Medical Microbiology, University of Pretoria, Republic of South Africa.
Zeis
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Anderson
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IF
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002991:Clofazimine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008010:Lichen Planus / Q000188:drug therapy; D008179:Lupus Erythematosus, Discoid / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D010894:Piroxicam / Q000031:analogs & derivatives / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism*
D007166:Immunosuppressive Agents; D013481:Superoxides; D010894:Piroxicam; D002991:Clofazimine; C032801:tenoxicam