endothelin-1 and Bronchitis

The recurrent bronchitis (RB) course is caused by the bronchi secretory-evacuation mechanisms state, which provide clearance from pathogens. This mechanism can be disrupted by vegetative reflexes and neuropeptides imbalance that develops in children with the syndrome of the vertebrobasilar arterial system (SVBAS). The objective: study of the neurogenic maintenance of the RB pathogenesis in children with SVBAS by studying the serum content of substances affecting of the bronchial mucosa secretory-evacuation function and inflammatory activity (substance P, vasoactive intestinal peptide - VIP and endothelin-1 - ET-1). 90 children aged 7 to 11 years were examined, 3 observation groups were formed: Group 1 - children with RB and SVBAS (n=30); Group 2 - children with SVBAS without RB (n=30); Group 3 - children with RB without SVBAS (n=30). In the Group 1, compared with the 2nd and 3rd, there was an increase in the children number with high serum content of substance P (by 66.7% and 50.0%, respectively, p<0.05) and ET -1 (by 23.3% and 40.0%, respectively, p<0.05), low content of VIP (by 46.7% and 23.4%, respectively, p<0.05). Children with RB and SVBAS have serum level imbalance of the pro-inflammatory substance P, ET-1 and anti-inflammatory VIP as the bronchitis severe course basis.

Topics: Bronchitis; Child; Endothelin-1; Humans; Substance P; Vasoactive Intestinal Peptide; Vertebrobasilar Insufficiency

Exposure to allergens or air pollutants often leads to asthma exacerbations associated with aggravation of airway inflammation. Although, repeated allergen challenge often induces chronic allergic airway inflammation (CAAI) and airway remodelling, yet, the effects of brief exposure to air pollutants such as SO(2) on development of CAAI and airway remodelling remain to be clarified.. The aim of the experiment was to investigate the effects of acute neutrophilic airway inflammation induced by brief exposure to SO(2) on development of CAAI and subepithelial fibrosis (SEF) in a murine model of asthma.. Acute airway inflammation was induced by brief exposure to 50 p.p.m. SO(2) (1 h/d, 3 days). CAAI and SEF in BALB/c mice were induced by repeated challenge with ovalbumin (OVA) for 5 or 9 weeks with or without prior exposure to SO(2). Bronchoalveolar lavage fluid (BALF) eosinophilia as index of CAAI, BALF endothelin-1 (ET-1) and TGF-beta1 levels, morphometric evaluation of fibrotic area beneath subbasement membrane and lung hydroxyproline content (Hyp) as indexes of SEF were monitored.. Exposure to SO(2) led to acute neutrophilic inflammation and epithelial sloughing with profound elevation of BALF ET-1. Repeated OVA challenge resulted in CAAI and SEF along with elevation of Hyp, increase of fibrotic area beneath subbasement membrane and elevation of BALF TGF-beta1. Preceding SO(2) exposure exaggerated BALF eosinophilia, facilitated and enhanced SEF with more significant elevation of BALF ET-1 and TGF-beta1 levels compared with OVA-challenged mice without prior exposure to SO(2). The increase of Hyp was positively correlated with elevation of BALF TGF-beta1 during CAAI (r=0.842, P<0.01).. This data demonstrated that SEF developed in parallel with severity and time course of CAAI following repeated OVA challenge. SO(2)-induced acute epithelial injury and neutrophilic inflammation could enhance CAAI and promote SEF, probably through overexpression of ET-1 and TGF-beta1.

Topics: Air Pollutants; Allergens; Animals; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Endothelin-1; Female; Lung; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; Pulmonary Fibrosis; Respiratory Mucosa; Sulfur Dioxide; Transforming Growth Factor beta

Endothelin-1 (ET-1) is a strong bronchoconstrictor which possesses pro-inflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET-1 synthesis, in an inflammation dominated by neutrophilic granulocytes, is as pronounced as previously demonstrated in an airway inflammation dominated by eosinophils. Moreover, the authors compared the production of ET-1 and tumour necrosis factor (TNF)-alpha in rat lungs following intratracheal instillation of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sephadex (SDX) (eosinophilic). The lung tissue ET-1 messenger ribonucleic acid (mRNA) expression was not increased in LPS treated animals whereas a six-fold increase was measured after 30 min in the SDX group (p<0.05). TNF-alpha mRNA signals increased early following LPS instillation, peaking at 2 h, whereas elevated TNF-alpha mRNA in the SDX model was observed at 24 h. The ET-1 concentrations in bronchoalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after both LPS and SDX exposure. At 24 h no further rise in ET-1 levels was observed in the LPS model, while a substantial increase in the ET-1 concentration was measured in the SDX group (p<0.05). The TNF-alpha concentrations in BALF rose considerably at 3 h in the LPS group, but was nearly abolished at 24 h. In SDX challenged animals however, an increase in BALF-TNF-alpha did not occur until 24 h postchallenge. In conclusion, intratracheal instillation of lipopolysaccharide, leading to a purely neutrophilic lung inflammation, does not induce synthesis of endothelin-1. This is in contrast to observations during an eosinophilic airway inflammation, indicating a specific role of endothelin-1 in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin-1 synthesis was observed by high levels of tumour necrosis factor-alpha in vivo.

Topics: Animals; Blotting, Northern; Bronchial Provocation Tests; Bronchitis; Bronchoalveolar Lavage Fluid; Dextrans; Disease Models, Animal; Endothelin-1; Eosinophilia; Lipopolysaccharides; Lung; Male; Probability; Rats; Rats, Wistar; Reference Values; Statistics, Nonparametric; Tumor Necrosis Factor-alpha