We examined the effects of doxofylline, which is a new methylxanthine analog, on heart rate, respiratory rate, respiratory resistance and airway responsiveness in five beagles, and compared with those effects of theophylline. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7Hz oscillation method). Theophylline (10 mg/kg, 20 mg/kg, 40 mg/kg) was orally administered one hour prior to the determination of airway responsiveness and doxofylline (20 mg/kg, 40 mg/kg, 80mg/kg) was orally administered thirty minutes prior to determination of airway responsiveness at intervals of about one week. Heart rate increased significantly by all dose of theophylline in a dose-dependent manner and by 80 mg/kg of doxofylline. Respiratory rate increased signficantly only by 40 mg/kg of theophylline. Respiratory resistance decreased significantly after administration of 40 mg/kg of theophylline. Airway responsiveness decreased significantly by 40 mg/kg of theophylline and 40 mg/kg, 80 mg/kg of doxofylline in a dose-dependent manner. These results suggest that doxofylline decreased airway responsiveness at the dosage which dose not affect the heart rate and respiratory rate compared with theophylline.

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Although eosinophils are generally thought to play a central role in the pathogenesis of asthma, there is a few evidence not to support this view. In order further to test this hypothesis, we studied whether the magnitude of eosinophil infiltration in the bronchial mucosa and their activation status are related to clinical manifestations. Bronchial biopsies were obtained from 15 symptomatic asthmatics, 17 asymptomatic asthmatics, 11 patients with asthma who had been taking oral prednisolone for at least 1 month, and 16 controls, then stained immunohistochemically with a EG2 monoclonal antibody. The serial sections were stained with Hansel. In 15 subjects, criostat sections were immunostained with anti CD3, CD4, CD8 and CD25 antibodies. There was a significant increase in the numbers of Hansel staining-positive cells, EG2 positive cells and % of EG2 positive cells in symptomatic asthmatics. There was a significant positive correlation between the numbers of Hansel-staining positive cells and CD3, CD4 and CD25 positive cells, and between the numbers of EG2 positive cells and CD4, CD25 positive cells. These results confirm the hypothesis that eosinophils play a key role in the pathogenesis of asthma, and T cells are controller cells in the recruitment and activation of eosinophils.

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The clinical significance of AlaSTAT (DPC) Specific IgE for Malassezia furfur (Mf) was evaluated by testing the sera of 147 atopic dermatitis (AD) patients. Patients were from 0 to 52 years old, and the prevalence of positive assay results was analyzed by age, class of reactivity, and degree of face and body symptoms. Evaluations of rhinitis, seborrhea as complications and serum total IgE by RIST were included. The prevalence of Mf specific IgE positive sera was lowest in the 0-2 year age group, and increased swiftly in the 3-9 year age group. The older age is, the higher specific IgE antibody for Mf. The prevalence in the 0-2 year age group was significantly different from the other age groups. Although none of the positive results were above AlaSTAT class 2 in the 0-2 year age group, the positive result above AIaSTAT class 2 increased in the 3-9 year age group and was highest in the older age groups, reaching a peak prevalence at age 20 years. A group of age 20 years or older prevalence was significantly different from the 3-9 and 10-19 years old patients. The prevalence of positive did not correlate with face and body symptoms. Adults were more often Mf positive than children. An increasing prevalence of severe face symptoms in adults did correlate with the increased prevalence of Mf specific IgE in the in sera. The AlaSTAT class 3 and 4 results correlated with more severe face symptoms, and complications by seborrhea. The high AlaSTAT class results also corresponded to high total IgE values.

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Allergen-specific lymphocyte proliferation was measured in 24 children with atopic dermatitis and 20 non-atopic controls. The level of house dust mite-specific S.I.F. (stimulation index measured by flow cytometry) in the atopic children was significantly higher than that in the non-atopic controls in every age-group, suggesting that the elevation of the mite-specific S.I.F. level is related to the development of atopic dermatitis. The level of house dust mite-specific S.I.F. correlated significantly with the level of house dust mite-specific IgE-RAST in older children (r = 0.73, p < 0.001), indicating that S.I.F. reflects the activity of lymphocytes competent to promote the production of IgE. In the atopic infants, there was no significant positive correlation between the levels of mite-specific S.I.F. and mite-specific IgE-RAST since, although the former was usually elevated, the latter was often very low or negative. The result suggests that the sensitization of T lymphocytes to house dust mite begins as early as in infancy prior to the development of mite-specific IgE antibody.

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In this study we investigated the effect of LTB_4 antagonist on eosinophil infiltration in skin and gut late phase response (LPR) in OVA-sensitized BALB/c mice. The eosinophil infiltrations to skin and gut induced by skin and oral challenge reached a peak at 12 h and 6 h after the challenge, respectively. Intraperitoneal administration of LTB_4 antagonist (ONO-4057) before the challenge significantly inhibited eosinophil infiltrations to the skin and gut by 53.3% and 73.7%, respectively (p < 0.05). Next, we investigated the effect to that by PAF antagonist (ONO-6240) and anti-IL-5 mAb in the skin system. OVA-induced eosinophil infiltration at 12 h after intracutaneous challenge was significantly inhibited by peritoneal administration of anti-IL-5 mAb before the challenge by 89.6% (p < 0.05), but not by that of PAF antagonist. Our results demonstrated the inhibitory effect of LTB_4 antagonist on eosinophil infiltration in skin and gut LPR, suggesting the potency of LTB_4 antagonist for treatment of skin lesion and food allergy in atopic dermatitis considered to be associated with LPR.

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