Immunomodulating effects of antibiotics: Literature review Translated title: Immunmodulierende Wirkungen von Antibiotika

The efficacy of low dose long-term erythromycin (EM) therapy in the treatment of chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB), has been reported, but its therapeutic mechanism is still unclear. In 13 patients receiving oral EM therapy the accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid was significantly reduced (p < 0.05), this reduction corresponds with an improvement in clinical symptoms. We sought to determine whether neutrophil chemotactic activity (NCA) in lavage fluid obtained from these 13 patients with DPB would respond to EM therapy. Pretreatment NCA in all patients was significantly elevated compared with levels in normal healthy nonsmoking volunteers (p < 0.001), and the level was greatly reduced after EM therapy (p < 0.001). In addition, this reduction correlated with increased percentages of neutrophils in the BAL fluid (r = 0.737, p < 0.01). Gel-filtration chromatography was also performed to characterize chemotactic factors. Pre-EM treatment BAL fluid revealed four NCA peaks (about molecular weight 15,000, 8,000, 1,500, and 300 daltons) in the elution profile, and chemotactic activity was reduced in all areas after EM therapy. These findings indicate that NCA in lavage fluid from patients with DPB consists of various components. Although it was not clear which component is predominantly affected, these results indicate that EM may inhibit the migration of neutrophils to inflammatory sites by reducing the intrapulmonary chemotactic gradient, thus, ultimately reducing pulmonary inflammation.

This study was designed to examine the possible mechanisms by which macrolide antibiotics favorably influence the clinical course of asthmatic patients. In the first set of experiments, we investigated the effect of roxithromycin (RXM), a newly synthesized macrolide antibiotic, on in vitro cytokine secretion by mitogen-activated human peripheral blood leukocytes. RXM suppressed the secretion of T cell cytokine interleukins (IL) 2-4 and monocyte cytokine tumor necrosis factor alpha. This inhibitory effects on cytokine secretion was dose dependent and firstly noted at a concentration of as little as 0.5 microgram/ml which is much lower than therapeutic blood levels. In the second part of experiments, we examined the influence of RXM on cytokine appearance in mouse lung extract induced by lipopolysaccharide (LPS) inhalation and on bronchial responsiveness to methacholine in LPS-treated mice. As compared with mice pretreated with phosphate-buffered saline, RXM administered orally at a single dose of 5 mg/kg once a day for 21 days inhibited the appearance of IL-3, IL-4, IL-5, and tumor necrosis factor alpha in aqueous lung extracts. Pretreatment with RXM also decreased the bronchial responsiveness to methacholine induced by intratracheal injection of LPS. We conclude that the attenuating effect of macrolide antibiotics on asthmatic syndromes might be explained partially by their inhibitory effects on cytokine secretion from leukocytes.