Article

Erythromycin prevents the pulmonary inflammation induced by exposure to cigarette smoke

Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Translational research : the journal of laboratory and clinical medicine 07/2011; 158(1):30-7. DOI: 10.1016/j.trsl.2011.03.001
Source: PubMed

ABSTRACT The effect of erythromycin on the inflammation caused by exposure to cigarette smoke was investigated in this study. Mice were exposed either to cigarette smoke or to environmental air (control), and some mice exposed to cigarette smoke were treated with oral erythromycin (100 mg/kg/day for 8 days). Pulmonary inflammation was assessed by determining the cellular content of bronchoalveolar lavage (BAL) fluid. The messenger RNA (mRNA) levels of various mediators, including keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, surfactant protein (SP)-D, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, interleukin (IL)-6 in lung tissue were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The exposure to cigarette smoke increased significantly the numbers of neutrophils (P = 0.029), macrophages (P = 0.029), and lymphocytes (P = 0.029) recovered in BAL fluid. Moreover, mRNA levels of KC (P = 0.029), MIP-2 (P = 0.029), SP-D (P = 0.029), and GM-CSF (P = 0.057) in the lung tissue were higher in mice exposed to cigarette smoke than in mice exposed to environmental air. In the erythromycin-treated mice that were exposed also to cigarette smoke, both neutrophil and lymphocyte counts were significantly lower in the BAL fluid than those in the vehicle-treated mice (P = 0.029). Erythromycin-treated mice exposed to cigarette smoke showed a trend of lower mRNA levels of KC and TNF-α in the lung tissue than those in the vehicle-treated mice, although the statistical significance was not achieved (P = 0.057). Our data demonstrated that erythromycin prevented lung inflammation induced by cigarette smoke, in parallel to the reduced mRNA levels of KC and TNF-α.

0 Followers
 · 
98 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: We investigated the effects of two antibiotics, erythromycin and rifampicin, on the immunomodulatory gene expression and cellular function of human polymorphonuclear leukocytes (PMNs). Methods: We used real-time quantitative PCR to examine the expression of immunomodulatory genes. The production of reactive oxygen species (ROS) was determined by fluorescence-activated cell sorting. PMN chemotaxis was analyzed using a KK chemotaxis chamber. Results: Stimulation of PMNs with lipopolysaccharide (LPS) resulted in increases in the mRNA levels of immunomodulatory genes. Rifampicin significantly inhibited the overexpression of TLR2, TLR4, CD14 and IL8Rs. However, erythromycin suppressed only the upregulation of TLR2 and TNFA. Neither antibiotic had an effect on the production of ROS. Rifampicin significantly inhibited PMN chemotaxis, but erythromycin had no effect. Conclusions: Erythromycin and rifampicin may play anti-inflammatory roles by affecting the expression levels of immunomodulatory genes or the chemotaxis of PMNs. © 2014 S. Karger AG, Basel.
    Chemotherapy 05/2014; 59(6):395-401. DOI:10.1159/000358818 · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on LPS-induced TNFalpha and/or CXCL8 release, PMA-induced MMP9 activity and NF-kappaB activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin and azithromycin in human monocytic U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNFalpha/CXCL8 production and MMP9 activity in U937 cells. In addition, SOL suppressed TNFalpha release and MMP9 activity in PBMC from COPD patients at 10microM, which is 100 times more potent than the other macrolides tested. Activated NF-kappaB due to oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia in vivo. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic, and may be a promising anti-inflammatory and anti-microbial macrolide for the treatment of COPD in the future.
    Journal of Pharmacology and Experimental Therapeutics 03/2013; 345(1). DOI:10.1124/jpet.112.200733 · 3.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract A formulation of tobacco extract containing 4% nicotine (TE) and similar nicotine formulation containing vehicle and 4% nicotine (NF) were evaluated using animal inhalation assays. Two 4-h inhalation exposures at 1 and 2 mg/L aerosol exposure concentrations, respectively, of the tobacco extract with 4% nicotine formulation showed that the LC50 was greater than 2 mg/L, the maximum concentration tested. All inhalation exposures were conducted using the capillary aerosol generator (CAG). Increasing aerosol TPM concentrations (0, 10, 50, 200, 1000 mg/m(3) TE and 0, 50, 200, 500, 1000 mg/m(3) NF) were generated via the CAG and used to expose groups of male and female rats for 4-h per day for 14 days. In life monitors for potential effects included clinical observations, weekly body weights and food consumption. Post mortem evaluations included gross tissue findings, hematology, clinical chemistry, serum plasma and nicotine levels, absolute and normalized organ and tissue weights, and histopathology of target organs. Treatment-related changes were observed in body weights, hematology, clinical chemistry, organ weights and histopathological findings for TE at the 200 and 1000 mg/m(3) exposure levels, and in the 500 and 1000 mg/m(3) exposure groups for NF. Under the conditions of these studies, the no-observed-adverse-effect level in the rat was approximately 50 mg/m(3) for the TE aerosol-exposed groups, and approximately 200 mg/m(3) in the NF aerosol-exposed groups.
    Inhalation Toxicology 03/2014; 26(4):207-21. DOI:10.3109/08958378.2013.878005 · 2.34 Impact Factor