Abstract
Ambroxol (Ax) is used as a mucolytics in the treatment of respiratory tract infections. Ax, at a general dose for humans, does not alter Chlamydia pneumoniae growth in mice. Therefore, we aimed to investigate the potential anti-chlamydial effect of Ax at a concentration four timed higher than that used in human medicine. Mice were infected with C. pneumoniae and 5-mg/kg Ax was administered orally. The number of recoverable C. pneumoniae inclusion-forming units (IFUs) in Ax-treated mice was significantly lower than that in untreated mice. mRNA expression levels of several cytokines, including interleukin 12 (IL-12), IL-23, IL-17F, interferon gamma (IFN-γ), and surfactant protein (SP)-A, increased in infected mice treated with Ax. The IFN-γ protein expression levels were also significantly higher in infected and Ax-treated mice. Furthermore, the in vitro results suggested that the ERK 1/2 activity was decreased, which is essential for the C. pneumoniae replication. SP-A and SP-D treatments significantly decreased the number of viable C. pneumoniae IFUs and significantly increased the attachment of C. pneumoniae to macrophage cells. Based on our results, a dose of 5 mg/kg of Ax exhibited an anti-chlamydial effect in mice, probably an immunomodulating effect, and may be used as supporting drug in respiratory infections caused by C. pneumoniae.
Highlights
The mice were infected with C. pneumoniae (2 × 105 inclusion-forming units (IFUs)/mouse); half of the mice were treated daily from day 1 pi with a 4× higher concentration of Ax (5 mg/kg) than the dose used as a mucolytics in common respiratory infections
Ax has been used as a medication since 1980 for treating respiratory infections; it was shown that Ax, at a normal dose used for humans, does not inhibit C. pneumoniae proliferation in mice
We found that C. pneumoniae-infected mice treated with four times higher doses of Ax than normal contained significantly fewer viable C. pneumoniae IFUs than those in untreated mice
Summary
Ambroxol (Ax; 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine) is widely used in the treatment of respiratory infections, chronic bronchitis, and neonatal respiratory distress syndrome due to its mucus viscosity-altering effect and has been shown to be a relatively safe drug [1,2]. Ax exhibits proinflammatory properties by elevating interleukin-10 (IL-10), IL-12, and interferon gamma (IFN-γ) expression; due to its aromatic moiety, Ax exhibits oxidant scavenger functions [4,5]. It has been reported that Ax elevates surfactant protein (SP) production and can reverse the lipopolysaccharide-stimulated induction of the extracellular signal-regulated kinase (ERK) 1/2 pathway [6,7]. Ax is used for the symptomatic treatment of sore throat during viral infections, as it shows local anesthetic effects [8,9]
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