Studies on the cause of intractable asthma using animal model Part 1. Establishment of a chronic asthma model by repeated antigen inhalation

To elucidate the cause of intractable asthma, guinea pigs were actively sensitized by intraperitoneal injection of ascaris suum as an antigen. We repeated the inhalation of aerosolized ascaris antigen eight times in the animal models which consisted of a non-treated group, a metopirone-treated group and a steroid-treated group. We investigated the course of asthmatic response by evaluating the ratio of expirations to inspirations after the inhalation challenge. The frequency of late asthmatic response (LAR) was increased by repeated inhalation of the antigen. There was no significant differnce in the frequency between non-treated group and steroid-treated group, but the metopirone-treated group showed strong LAR compared with the other two groups. The intensity of LAR was gradually increased and that of immediate asthmatic response (LAR) was decreased in the metopirone-treated group. Finally, we established a chronic asthma model in which LAR was strong and the asthma attack was prolonged over twenty-four hours. These results suggest that the model will be useful in clarifying the causes of intractable asthma in humans

Studies on the cause of intractable asthma using animal model Part 2. Immunoglobulin G, chemical mediators and cell reactions in BALF and peripheral blood of chronic asthma model

To clarify the mechanism of intractable asthma, we examined the cellular content and chemical mediators in BALF and peripheral blood of a chronic asthma model which we had already established by inhalation of ascaris suum antigen. The serum levels of antigen specific IgG antibody on the eighth day were signicantly higher than those before inhalation. The serum levels of antigen specific IgG(1) antibody increased on the eighth day compared with levels before inhalation. The serum levels of antigen specific IgG(2) antibody as a blocking antibody increased and immediat asthmatic response (IAR) gradually improved until the fourth day. The number of eosinophils after eight days of inhalation was decrease in peripheral blood but was significantly increased in BAL and lung tissue. The serum levels of LTC(4) after eight days of inhalation decreased significanlty compared to those after one day of inhalation. LTB4 concentration in BAL after eight days of inhalation were significanlty lower than those after one day of inhalation. Histamine concentrations were increased in BAL in both the IAR and dual asthmatic response (DAR) animal model. These data suggest that intractable asthma was induced by many kinds of chemical mediators produced by inflammatory cells including eosinophils, mast cell-basophils, neutrophils and lymphocytes

Studies on the cause of intractable asthma using animal model Part 1. Establishment of a chronic asthma model by repeated antigen inhalation

To elucidate the cause of intractable asthma, guinea pigs were actively sensitized by intraperitoneal injection of ascaris suum as an antigen. We repeated the inhalation of aerosolized ascaris antigen eight times in the animal models which consisted of a non-treated group, a metopirone-treated group and a steroid-treated group. We investigated the course of asthmatic response by evaluating the ratio of expirations to inspirations after the inhalation challenge. The frequency of late asthmatic response (LAR) was increased by repeated inhalation of the antigen. There was no significant differnce in the frequency between non-treated group and steroid-treated group, but the metopirone-treated group showed strong LAR compared with the other two groups. The intensity of LAR was gradually increased and that of immediate asthmatic response (LAR) was decreased in the metopirone-treated group. Finally, we established a chronic asthma model in which LAR was strong and the asthma attack was prolonged over twenty-four hours. These results suggest that the model will be useful in clarifying the causes of intractable asthma in humans