thromboxane-b2 and Bronchitis

To investigate the mechanisms of airway hyperresponsiveness (AHR), we examined the time course for asthmatic responses (including immediate asthmatic response (IAR), late asthmatic response (LAR), and AHR), airway inflammation (including edema in the airway, accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF), and mediator release including histamine and thromboxane A2 (TXA2) in BALF after the repeated provocation of aeroantigen in sensitized guinea pigs. Furthermore, we examined the effect of S-1452, a TXA2 receptor antagonist, on the antigen-induced airway obstruction and AHR in guinea pigs. We found that IAR occurred 1 min after every antigen inhalations. LAR was observed every 4 h after the inhalation of antigen without 1st or 2nd challenge. AHR was initially observed 4 h after the 5th inhalation of antigen, and then AHR was observed at every time measured even after the 6th provocation. The water content of the airway increased after the 2nd antigen inhalation. A number of leukocytes, especially eosinophils in BALF, was observed 30 min after the 2nd antigen inhalation. Desquamation of epithelia was observed 30 min after the 5th antigen inhalation. TXB2 and histamine in BALF were detected after the first antigen inhalation. These results suggest that LAR is caused by repeated airway inflammation such as eosinophilia and mediator release including TXA2. AHR may appear with the damages of lung tissue such as desquamation of epithelia. Oral administration of S-1452 (1 and 10 mg/kg) significantly inhibited LAR and AHR, assessed after the 6th antigen challenge. The present findings suggest that repeated antigen challenge causes airway inflammation and leads to the onset of LAR and AHR when became chronic. Furthermore, persistent generated TXA2 plays an important role in the pathogenesis of antigen-induced late-phase obstruction and AHR.

Topics: Airway Obstruction; Airway Resistance; Animals; Antigens; Asthma; Bridged Bicyclo Compounds; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchitis; Bronchoalveolar Lavage Fluid; Fatty Acids, Monounsaturated; Guinea Pigs; Histamine; Male; Prostaglandin Antagonists; Pulmonary Edema; Thromboxane B2; Time Factors

Serum cortisol levels and bronchoalveolar lavage fluid (BALF) from 105 patients with chronic obstructive pulmonary disease (COPD) and 36 normal subjects were examined and the relationship between cortisol inhibiting the TXB2 secreted by alveolar macrophage (AM) and the theory of Syndrome Differentiation in TCM was explored. Results showed: (1) No significant differences were found between chronic bronchitis and normal subjects on cortisol levels in serum, but in BALF, cortisol levels was significantly lower in Lung Qi Deficiency when compared with that in normal subjects. (2) the levels of cortisol inhibiting the TXB2 secreted by AM which were significantly lower in chronic bronchitis when compared with that in control. In short, the amount and function of cortisol in BALF were significantly different in various syndromes in TCM of chronic bronchitis.

Topics: Adult; Aged; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Diagnosis, Differential; Female; Humans; Hydrocortisone; Macrophages, Alveolar; Male; Medicine, Chinese Traditional; Middle Aged; Thromboxane B2; Yin Deficiency

A study was made of the content of leukotriene B4, prostacycline and thromboxane A2 in the fluid of bronchoalveolar lavage in 62 patients with chronic bronchitis (CB) in the stage of exacerbation and remission. The time course of changes in the concentration of the eukosanoids was compared with the status of pulmonary local defense factors and cellular immunity. In catarrhal obstructive bronchitis, an important mechanism of a steady maintenance of bronchial obstruction involved a rise of the content of leukotriene B4 whereas in purulent obstructive bronchitis, it was an excess level of thromboxane A2. It is assumed that immunologically dependent activation of the leukotriene B4 and thromboxane synthetase capacity of alveolar macrophages may stipulate the clinical course of CB, modulating the bronchoconstrictor or inflammatory component of the disease. To correct phlogogenous function of alveolar macrophages, the use of immunomodulating therapy with a selective action on the suppressor component of immunity is desirable.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Chronic Disease; Epoprostenol; Humans; Immunity, Cellular; Leukotriene B4; Middle Aged; Thromboxane A2; Thromboxane B2

Septicemia by gram-negative organisms is a common cause of the adult respiratory distress syndrome (ARDS). The role of neutrophils in causing parenchymal lung damage in ARDS has recently been emphasized. A single intraperitoneal injection of Escherichia coli endotoxin in rats causes acute neutrophil alveolitis similar to that of ARDS. We studied the ability of pretreatment with either ibuprofen (IBU) or methylprednisolone (MP) to ablate directly the alveolar inflammatory response to endotoxin in the rat model. To compare the severity of inflammation, we quantified inflammatory cell recovery by whole lung lavage 24 hours after injection of endotoxin, the time point at which neutrophil alveolitis due to endotoxin is most intense. Pretreatment with a single dose of IBU 3.75 mg/kg prior to endotoxin injections was associated with a significant increase in the total number of inflammatory cells, and in both the percentage and the absolute number of neutrophils recovered from the lung, despite significantly decreasing the plasma level of thromboxane B2, which increased 10-fold after endotoxin. Paradoxically, IBU 30 mg/kg significantly decreased the intensity of neutrophil alveolitis. MP 30 mg/kg had no effect on recovery of inflammatory cells from the lung by bronchoalveolar lavage following endotoxin. Cyclooxygenase inhibitors such as ibuprofen may cause a dose-dependent biphasic effect on lung inflammation following endotoxin: enhancement of inflammation at a low dose and suppression of inflammation at a high dose.

Topics: Animals; Bronchitis; Gram-Negative Bacteria; Ibuprofen; Leukocyte Count; Methylprednisolone; Neutrophils; Rats; Rats, Inbred Strains; Respiratory Distress Syndrome; Shock, Septic; Thromboxane B2; Time Factors