Clindamycin, erythromycin, and roxithromycin inhibit the proinflammatory interactions of Pseudomonas aeruginosa pigments with human neutrophils in vitro.
The Pseudomonas aeruginosa-derived phenazine pigments pyocyanin and 1-hydroxyphenazine (1-hp) prime human neutrophils for enhanced, stimulus-activated release of superoxide and myeloperoxidase (MPO), respectively. In the present study, the modulatory potentials of the antimicrobial agents clindamycin, erythromycin, and roxithromycin (10 and 20 micrograms/ml) on the prooxidative interactions of pyocyanin and 1-hp (12.5 microM) with human neutrophils have been investigated. Clindamycin, erythromycin, and especially roxithromycin caused dose-related inhibition of the generation of superoxide by both untreated and pyocyanin-treated neutrophils during activation with either the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) or the calcium ionophore A23187. The antimicrobial agents also inhibited the generation of reactive oxidants by the MPO-H2O2-halide system during activation of both untreated and 1-hp-treated neutrophils by FMLP. These effects appeared to be due to drug-related interference with membrane-associated oxidative metabolism, since none of the antimicrobial agents inhibited the release of MPO by activated neutrophils, nor did they possess oxidant-scavenging properties. These data demonstrate that clindamycin, erythromycin, and especially roxithromycin antagonize the proinflammatory interactions of pyocyanin and 1-hp with neutrophils and indicate a possible therapeutic role for these antimicrobial agents in the prevention of tissue damage in diseases characterized by P. aeruginosa infection.
Ras
G J
GJ
Department of Immunology, University of Pretoria, South Africa.
Anderson
R
R
Taylor
G W
GW
Savage
J E
JE
van Niekerk
E
E
Joone
G
G
Koornhof
H J
HJ
Saunders
J
J
Wilson
R
R
Cole
P J
PJ
D002981:Clindamycin / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D009195:Peroxidase / Q000494:pharmacology; D010619:Phenazines / Q000494:pharmacology; D010860:Pigments, Biological / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000187:drug effects; D011710:Pyocyanine / Q000494:pharmacology; D015575:Roxithromycin / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D010619:Phenazines; D010860:Pigments, Biological; D013481:Superoxides; D015575:Roxithromycin; D002981:Clindamycin; C050093:1-hydroxyphenazine; D004917:Erythromycin; D011710:Pyocyanine; D009195:Peroxidase