tetracycline and Pulmonary-Fibrosis

Inhalation of dust containing silica particles is associated with severe pulmonary inflammation and lung injury leading to chronic silicosis including fibrotic remodeling of the lung. Silicosis represents a major global health problem causing more than 45.000 deaths per year. The inflammasome-caspase-1 pathway contributes to the development of silica-induced inflammation and fibrosis via IL-1β and IL-18 production. Recent studies indicate that tetracycline can be used to treat inflammatory diseases mediated by IL-1β and IL-18. Therefore, we hypothesized that tetracycline reduces silica-induced lung injury and lung fibrosis resulting from chronic silicosis via limiting IL-1β and IL-18 driven inflammation.. To investigate whether tetracycline is a therapeutic option to block inflammasome-caspase-1 driven inflammation in silicosis, we incubated macrophages with silica alone or combined with tetracycline. The in vivo effect of tetracycline was determined after intratracheal administration of silica into the mouse lung.. Tetracycline selectively blocks IL-1β production and pyroptotic cell death via inhibition of caspase-1 in macrophages exposed to silica particles. Consistent, treatment of silica-instilled mice with tetracycline significantly reduced pulmonary caspase-1 activation as well as IL-1β and IL-18 production, thereby ameliorating pulmonary inflammation and lung injury. Furthermore, prolonged tetracycline administration in a model of chronic silicosis reduced lung damage and fibrotic remodeling.. These findings suggest that tetracycline inhibits caspase-1-dependent production of IL-1β in response to silica in vitro and in vivo. The results were consistent with tetracycline reducing silica-induced pulmonary inflammation and chronic silicosis in terms of lung injury and fibrosis. Thus, tetracycline could be effective in the treatment of patients with silicosis as well as other diseases involving silicotic inflammation.

Topics: Animals; Caspase 1; Caspase Inhibitors; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Pneumonia; Protein Synthesis Inhibitors; Pulmonary Fibrosis; Silicon Dioxide; Tetracycline

The activity of amoxycillin, amoxycillin/clavulanic acid and two tetracycline antibiotics was investigated against three strains of Chlamydia trachomatis in vitro. McCoy cells were infected and single doses of antibiotic administered 24 h after infection. The percentage of infected cells was calculated at intervals up to 72 h after infection. Amoxycillin and clavulanic acid, alone and in combination, reduced the incidence of inclusion formation of all three strains. Particularly good activity was observed against the laboratory-adapted strain C. trachomatis Sa2f and a clinical isolate C. trachomatis LB1, where a progressive reduction in numbers of inclusions was observed with time. Minocycline and oxytetracycline were the most active agents tested. In an experimental animal model, mice were inoculated intranasally with C. trachomatis MoPn (ATCC VR123) which caused a fatal pneumonia within 16 days, and treated orally for four days commencing at 24 h after infection. At doses producing clinically achievable serum concentrations, amoxycillin (10 mg/kg), amoxycillin/clavulanic acid (10 + 5 mg/kg) and minocycline (5 mg/kg) all protected the mice over a 21-day period. The majority of the animals treated with clavulanic acid alone (20 mg/kg) survived the infection. Treatment with oxytetracycline was less effective, a dose of 160 mg/kg being required to protect 70% of the mice. The results indicate that amoxycillin and amoxycillin/clavulanic acid were more effective against C. trachomatis MoPn in vivo than might be predicted from in-vitro data, suggesting that amoxycillin/clavulanic acid may have potential for the treatment of polymicrobial infections involving C. trachomatis.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Chlamydia Infections; Chlamydia trachomatis; Clavulanic Acids; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Mice; Microbial Sensitivity Tests; Oxytetracycline; Pulmonary Fibrosis; Tetracycline

Topics: Drug Hypersensitivity; Female; Humans; Iatrogenic Disease; Long-Term Care; Middle Aged; Nitrofurantoin; Pulmonary Fibrosis; Radiography; Steroids; Tetracycline

Topics: Blood Sedimentation; Body Weight; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Infant; Infant, Newborn; Leukocyte Count; Lung Diseases; Male; Pulmonary Fibrosis; Staphylococcal Infections; Staphylococcus; Tetracycline

Topics: Adolescent; Adrenal Cortex Hormones; Aminopyrine; Blood; Blood Cell Count; Blood Transfusion; Capillaries; Child; Child, Preschool; Cyanosis; Dyspnea; Female; Humans; Lanatosides; Leukemia; Male; Methotrexate; Methylprednisolone; Nystatin; Penicillins; Plasma Cells; Prednisone; Pulmonary Circulation; Pulmonary Fibrosis; Purines; Tetracycline

Topics: Adenoviridae Infections; Anti-Bacterial Agents; Bronchopneumonia; Child; Cortisone; Erythromycin; Humans; Infant; Influenza, Human; Penicillins; Plasma Cells; Pneumonia; Pneumonia, Pneumocystis; Pneumonia, Rickettsial; Pneumonia, Viral; Psittacosis; Pulmonary Fibrosis; Q Fever; Streptomycin; Tetracycline