Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release

Abstract

Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis.A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre-and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8.There were significant (p<0.05) pre-to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post-minus pre-exposure value for these variables.The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables. Eur Respir J 2000; 15: 856±862.

Modification by antioxidant supplementation of changes in human lung function associated with air pollutant exposure: A systematic review

“…Such realistic exposures are more representative and informative than studies conducted under controlled exposure conditions, such as those in Table 1. All of the uncontrolled exposure studies concluded that a potential benefit for antioxidant supplementation in attenuating the negative effects of air pollution is evident; these findings are consistent with previous studies investigating the role of various anti-inflammatory interventions, for example azithromycin [37], indomethacin [38], cyclooxygenase metabolites [39] and budesonide [40] on pollution induced lung outcome. However, such consistency does not refute the need for more research on the subject.…”

Azithromycin Inhibits Mucus Hypersecretion from Airway Epithelial Cells

“…Several animal studies demonstrated that AZM attenuated many types of experimental airway inflammation caused by the allergic inflammation [15], by the inhalation of irritant gas, ozone [16], by the lung ischemia reperfusion injury [17], or by bacterial and viral infections [18, 19] in lower airways. In the present study, AZM also attenuated antigen- or LPS-induced mucus production in rat nasal epithelium.…”

Inhibition of myristoylated alanine-rich C kinase substrate (MARCKS) protein inhibits ozone-induced airway neutrophilia and inflammation

“…Similarly, neutralizing antibodies to IP-10, KC/IL-8, and monocyte chemoattractant protein (MCP)-3 also deplete ozone-mediated airway neutrophilia in murine studies [37]. Contrary to the effects of macrolides in minimizing airway neutrophilia in multiple species, azithromycin administration has little effect on altering ozone-induced BAL fluid neutrophils [38]. In a recent study, the unprecedented ability of a novel 24–amino acid peptide (MANS, homologous to N-terminal of MARCKS protein) to substantially inhibit fMLF-( N -formyl-methionyl-leucyl-phenylalanine)–mediated neutrophil migration in vitro has been reported [39].…”