title: Apoptosis, oxidative metabolism and interleukin-8 production in human neutrophils exposed to azithromycin: effects of Streptococcus pneumoniae.
abstract: Pathogen virulence factors and the host inflammatory response cause tissue injury associated with respiratory tract infections. The azalide azithromycin has demonstrated efficacy in the treatment of these infections. It has been demonstrated previously that induction of polymorphonuclear leucocyte (PMN) apoptosis is associated with minimization of tissue damage and inflammation in the lung. We hypothesized that, in addition to its antibacterial effects, azithromycin may promote apoptosis. The aim of the study was to determine the effects of azithromycin on PMN apoptosis, oxidative function and interleukin-8 (IL-8) production in the presence or absence of Streptococcus pneumoniae, in comparison with penicillin, erythromycin, dexamethasone or phosphate-buffered saline. Human circulating PMNs were assessed for apoptosis (by annexin V labelling and ELISA), oxidative function (by nitroblue tetrazolium reduction) and IL-8 production (by ELISA). Azithromycin significantly induced PMN apoptosis in the absence of S. pneumoniae after 1 h (10.27% +/- 1.48%, compared with 2.19% +/- 0.42% in controls) to levels similar to those after 3 h induction with tumour necrosis factor-alpha (8. 73% +/- 1.86%). This effect was abolished in the presence of S. pneumoniae. Apoptosis in PMNs exposed to the other drugs was not significantly different from that in controls. Azithromycin did not affect PMN oxidative metabolism or IL-8 production. In summary, azithromycin-induced PMN apoptosis may be detected in the absence of any effect on PMN function, and the pro-apoptotic properties of azithromycin are inhibited in the presence of S. pneumoniae.
authors.affiliation: Department of Biological Sciences, The University of Calgary, Alberta, Canada, T2N 1N4.
authors.forename: C C
authors.initials: CC
authors.lastname: Koch
authors.forename: D J
authors.initials: DJ
authors.lastname: Esteban
authors.forename: A C
authors.initials: AC
authors.lastname: Chin
authors.forename: M E
authors.initials: ME
authors.lastname: Olson
authors.forename: R R
authors.initials: RR
authors.lastname: Read
authors.forename: H
authors.initials: H
authors.lastname: Ceri
authors.forename: D W
authors.initials: DW
authors.lastname: Morck
authors.forename: A G
authors.initials: AG
authors.lastname: Buret
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D017963:Azithromycin / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D013296:Streptococcus pneumoniae / Q000502:physiology*
chemical_list: D016209:Interleukin-8; D017963:Azithromycin