Erythromycin Modulates Eosinophil Chemotactic Cytokine Production by Human Lung Fibroblasts in Vitro

Abstract

Recent studies suggest that erythromycin can suppress the production of some cytokines and may be an effective treatment for asthma. Eosinophil chemotactic cytokines have been suggested to contribute to the pathogenesis of asthma by the recruitment of eosinophils. We hypothesized that erythromycin modulates eosinophil chemotactic cytokine production. To test the hypothesis, we evaluated the potential of erythromycin to modulate the release of eosinophil chemoattractants from the human lung fibroblast cell line HFL-1. HFL-1 released eotaxin, granulocyte-macrophage colony-stimulating factor, and regulated and normal T-cell expressed and presumably secreted (RANTES) in response to interleukin-1␤ or tumor necrosis factor alpha. Erythromycin attenuated the release of these cytokines and eosinophil chemotactic activity by the HFL-1. The suppressive effect on eotaxin was the most marked of these cytokines. Erythromycin therapy also suppressed eotaxin mRNA significantly. These results suggest a mechanism that may account for the apparent beneficial action of macrolide antibiotics in the treatment of allergic airway disorders.

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

“…Similar effects were reported in another study, along with inhibition of IL-8 levels in nasal lavage fluid, which was thought to drive polyp growth (330). Clarithromycin dose dependently reduced the expression of IL-8 and NF-B in human adenoidal fibroblasts (279), and erythromycin significantly decreased TNF-␣-induced eotaxin mRNA as well as eotaxin release from human lung fibroblasts (245). EM703, a novel derivative of erythromycin A (discussed below), inhibited fibroblast proliferation and collagen production in the murine lung fibroblast cell line MLg2908 treated with TGF-␤ (170).…”

“…Macrolides inhibit secretion of the eosinophil-chemotactic cytokines RANTES and eotaxin (245). Erythromycin significantly decreased TNF-␣-induced eotaxin mRNA as well as eotaxin release from human lung fibroblasts.…”

Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial

“…It has been shown that a correlation exists between numbers of mast cells, eosinophils and neutrophils and the degree of airway hyperresponsiveness [27]. It has been further shown that enhanced IL-4, IL-8 and eotaxin levels have a role in the development of airway inflammation and hyperresponsiveness [28][29][30]. PITREZ et al [31] suggested that there were significant correlations between IL-4 levels in blood and airway secretions.…”

“…Eotaxin is highly specific for eosinophil recruitment [30]. Macrolides attenuate the release of eotaxin, granulocyte-macrophage colony-stimulating factor and RANTES [30].…”

“…Lung fibroblasts are an important source of eosinophil chemotactic activity. Inhibitory effects of erythromycin on eosinophil chemotactic cytokine release by lung fibroblasts may be one of the mechanisms of decreased airway hyperresponsiveness and the resulting amelioration of disease activity following therapy with that agent [30]. Macrolides may also protect epithelial cells at inflamed sites by inhibiting the release of reactive oxygen species from eosinophils [44].…”