Inhibitory effect of erythromycin on interleukin 8 production by 1 alpha,25-dihydroxyvitamin D3-stimulated THP-1 cells

Abstract

We have recently reported that long-term administration of erythromycin at a low dose reduced the number of neutrophils and concentrations of interleukin 8 (IL-8) in bronchoalveolar lavage fluid in patients with chronic lower respiratory tract disease. To investigate the mechanism of action of erythromycin, we evaluated its effect on IL-8 production in the 1 alpha,25-dihydroxyvitamin D3-stimulated human monocytic cell line THP-1. Erythromycin at a concentration of 10 micrograms/ml significantly reduced IL-8 production by THP-1 cells stimulated with lipopolysaccharide (10 ng/ml) and 1% normal human serum compared with the amount produced by untreated cells (untreated cells, 2,448 pg/ml; erythromycin-treated cells, 872 pg/ml). Our results suggest that erythromycin may impair IL-8 production by alveolar macrophages, ultimately reducing neutrophil accumulation in the airspace.

Clinical implications of the immunomodulatory effects of macrolides

“…Although the mechanism by which macrolides inhibit the accumulation of neutrophils and reduce inflammation is not clear, studies show that macrolides significantly affect a variety of these immune mediators and transcription factors. 13,14,23,25,29,47,48 Expression of IL-8 messenger RNA in alveolar macrophages, epithelial cells, and endothelial cells suggests that IL-8 is produced in the lung and is an important mediator in the accumulation of neutrophils and the inflammatory response. In vitro studies suggest that macrolides impair the production of IL-8 by human alveolar macrophages, which results in the reduction of neutrophil accumulation.…”

“…In vitro studies suggest that macrolides impair the production of IL-8 by human alveolar macrophages, which results in the reduction of neutrophil accumulation. 29 Only the 14-member macrolides-erythromycin, clarithromycin, and roxithromycin-were effective in inhibiting the production of IL-8. The 16-member macrolides-josamycin and midecamycin-and the nonmacrolide drugs-piperacillin, clindamycin, and ciprofloxacin-had no effect on the production of IL-8.…”

“…Macrolides may decrease the volume of mucus secreted in patients with chronic airway disease by direct actions on mucus-producing cells in the airways or indirectly by decreasing bacterial adhesion, cytokine production, inflammatory cell recruitment, or the generation of free radicals. [23][24][25][26][27][28][29] Macrolides may also decrease sputum production by inhibiting water secretion into the airway lumen by inhibiting secretion of chloride. 30,31 Macrolides directly inhibit acetylcholineevoked Cl -channels in vitro, which may explain the activity of these drugs even in patients with cystic fibrosis who have a defect in the cystic fibrosis transmembrane conductance regulator, a cyclic adenosine monophosphate-regulated chloride channel.…”

Comparative uptake of grepafloxacin and ciprofloxacin by a human monocytic cell line, THP-1

“…2 THP-1 is a human monocytic cell line 9 which matures into macrophage-like cells following stimulation with phorbol 12 myristate 13-acetate (PMA) 10 or 1 α, 25-dihydroxy vitamin D3. 11 Cirillo et al 12 reported that Legionella pneumophila could invade and multiply in THP-1 cells in a manner similar to its behavior in human monocytes and macrophages.…”

Macrolide antibiotics induce apoptosis of human peripheral lymphocytes in vitro

“…More recently they have been used in the treatment of infections by Helicobacter pylori and non-tuberculous mycobacterial lung diseases and they are also reported to have motor-stimulating activity [1,2]. In addition to the above actions, MCL exhibit anti-inflammatory activity, such as inhibiting lymphocyte function [3,4], promoting monocyteto-macrophage differentiation [5], modulating interleukin (IL)-8 expression/production [6,7] and inhibiting chloride and glycoconjugate secretion [8,9]. These actions may account for its clinical effectiveness in the treatment of chronic inflammatory diseases, such as diffuse panbronchiolitis (DPB) [10,11].…”