Therapeutic effects of recombinant human interleukin-1 receptor antagonist on toluene-2, 4-diisocyanate-induced guinea pig allergic rhinitis model / 国际药学研究杂志

Objective To evaluate the effects of the recombinant human interleukin-1 receptor antagonist(rhIL-1ra)on a toluene-2, 4-diisocyanate (TDI)-induced guinea pig allergic rhinitis (AR)model. Methods An AR model was established via sensitization and challenge of two-step procedure using TDI in guinea pigs. Normal animals were treated only with the olive oil(TDI vehicle). Sixty adult guinea pigs were randomly divided into six groups (n=10): normal group, model group (rhIL-1ra vehicle), positive control group (budesonide, 25.6 µg/kg), rhIL-1ra treated groups (rhIL-1ra 50, 100 and 200 µg/kg, respectively). From day 8 after sensitization, animals of all the groups were treated respectively with the agents or vehicle once a day for 14 days. During the observation period, the index of clinic score was recorded for every animal. At day 14 of the dosing, guinea pigs were sacrificed 30 min after the last TDI challenge and observation. Blood samples were taken from the abdominal aorta to prepare the serum for detection of histamine, and the nasal mucosase were dissected for histamine detection and histopathological observation. Results Compared with the guinea pigs in normal group, those in the model group exerted the typical symptoms of AR. It was shown that rhIL-1ra could improve nasal symptoms and cause a significant decrease in the instances of nasal sneezing as well. In addition, rhIL-1ra significantly reduced the concentrations of histamine in the nasal mucosa and IgE in the blood compared with those in the model group (P<0.05). Moreover, the pathological results showed that less edema, vasodilation and inflammatory cell infiltration were found in the nasal mucosa after rhIL-1ra application. Budesonide also showed the above effects with no significant difference compared with rhIL-1ra. Conclusion A guinea pig allergic rhinitis model is successfully induced by TDI. The results indicated that rhIL-1ra(50-200 µg/kg)is effective in improving allergic rhinitis. Our findings indicated that rhIL-1ra might serve as a potential new drug for allergic rhinitis therapy.

Therapeutic effects of recombinant human interleukin-1 receptor antagonist on toluene-2,4-diisocyanate-induced guinea pig allergic rhinitis model / 国际药学研究杂志

Objective To evaluate the effects of the recombinant human interleukin-1 receptor antagonist(rhIL-1ra)on a tol?uene-2,4-diisocyanate(TDI)-induced guinea pig allergic rhinitis (AR)model. Methods An AR model was established via sensiti?zation and challenge of two-step procedure using TDI in guinea pigs. Normal animals were treated only with the olive oil(TDI vehicle). Sixty adult guinea pigs were randomly divided into six groups(n=10):normal group,model group(rhIL-1ra vehicle),positive con?trol group(budesonide,25.6μg/kg),rhIL-1ra treated groups(rhIL-1ra 50,100 and 200μg/kg,respectively). From day 8 after sensi?tization,animals of all the groups were treated respectively with the agents or vehicle once a day for 14 days. During the observation pe?riod,the index of clinic score was recorded for every animal. At day 14 of the dosing,guinea pigs were sacrificed 30 min after the last TDI challenge and observation. Blood samples were taken from the abdominal aorta to prepare the serum for detection of histamine , and the nasal mucosase were dissected for histamine detection and histopathological observation. Results Compared with the guinea pigs in normal group,those in the model group exerted the typical symptoms of AR. It was shown that rhIL-1ra could improve nasal symptoms and cause a significant decrease in the instances of nasal sneezing as well. In addition,rhIL-1ra significantly reduced the concentrations of histamine in the nasal mucosa and IgE in the blood compared with those in the model group(P<0.05). Moreover, the pathological results showed that less edema,vasodilation and inflammatory cell infiltration were found in the nasal mucosa after rhIL-1ra application. Budesonide also showed the above effects with no significant difference compared with rhIL-1ra. Conclusion A guinea pig allergic rhinitis model is successfully induced by TDI. The results indicated that rhIL-1ra(50-200μg/kg)is effective in im?proving allergic rhinitis. Our findings indicated that rhIL-1ra might serve as a potential new drug for allergic rhinitis therapy.

IL-4 and IL-5 Secretions Predominate in the Airways of Wistar Rats Exposed to Toluene Diisocyanate Vapor / 예방의학회지

OBJECTIVES: We established a Wistar rat model of asthma caused by toluene diisocyanate (TDI) exposure, and investigated the relationship between TDI exposure concentrations and respiratory hypersensitivity, airway inflammation, and cytokine secretions in animals, to better understand the mechanism of TDI induced occupational asthma. METHODS: Wistar rats were exposed to two different concentrations of TDI vapor four hours a day for five consecutive days. Bronchoalveolar lavage (BAL) was performed, and differential leucocytes from the BAL fluid were analyzed. Lung histopathological examination was carried out to investigate the inflammatory status in the airways. Production of cytokines interleukin (IL)-4 and IL-5 productions in the BAL fluid in vivo was determined with enzyme-linked immunosorbent assay kits. RESULTS: The TDI-exposed rats exhibited greater airway hypersensitivity symptoms than the control rats. The BAL differential cell count and lung histopathological examination demonstrated that inflammation reactions were present in both the central and peripheral airways, characterized with marked infiltration of eosinophils in the TDI-exposed rats. The cytokine assay showed that IL-4 and IL-5 were predominantly produced in the BAL fluid in vivo. CONCLUSIONS: These findings imply that TDI exposure concentrations may greatly affect the occurrence and extent of inflammatory events and that Th2 type cytokines may play an important role in the immunopathogenesis of TDI-induced occupational respiratory hypersensitivity.

Acute and Chronic Changes of Vascular Endothelial Growth Factor (VEGF)in Induced Sputum of Toluene Diisocyanate (TDI)-induced Asthma Patients

Vascular endothelial growth factor (VEGF) is a multi-functional cytokine involved in inflammation, repair and angiogenesis in asthmatic airway. This study aimed to evaluate the role of VEGF in immediate bronchoconstriction induced by TDI inhalation, and in chronic TDI-asthma patients. 11 newly diagnosed TDI-asthma patients (group I), 12 chronic TDI-asthma patients with persistent asthma symptoms followed for >4 yr and 15 unexposed healthy controls were enrolled. In group I, induced sputum and serum were collected before and 7 hr after placebo- and TDI-bronchoprovocation test (BPT). In group II, induced sputum and serum were collected every 2 yr. VEGF levels were measured by ELISA. There were no significant differences in sputum and serum VEGF levels between patients and controls. Before and after placebo and TDI-BPT, no significant changes were noted in sputum and serum VEGF levels of group I. In group II patients, sputum VEGF showed variable changes at 1-yr, then decreased significantly at 2-yr (p<0.05), while serum VEGF showed variable changes at 2-yr, which decreased significantly at 4-yr (p<0.05). These results suggest that VEGF may play a minor role in immediate bronchoconstriction after TDI-BPT. In chronic TDI-asthma, VEGF may be involved to 2 yr after the diagnosis and the contribution may decrease after then.

EFFECTS OF EXERCISE AND <I>SPIRULINA PLATENSIS</I> (SPL) INTAKE ON HAPTEN SPECIFIC IMMUNE RESPONSE OF GROWING MICE / 体力科学

A study was performed to investigate the effects of exercise and <I>Spirulina platensis</I> (SPL) intake on the hapten specific immune response of growing mice.<BR>Male BALB/C mice aged five weeks were divided into 6 groups : Group A was a control group given a normal diet ; group B, sedentary with a normal diet ; group C, exercise with a normal diet ; group D, control with SPL diet ; group E, sedentary with a SPL diet ; group F, exercise with a SPL diet. The mice in groups C and F were trained by swimming for about 30 min 4 times a week for 5 weeks. The SPL diet was a mixture of SPL (20%) and the normal diet (80%) . At 4 weeks after the experiment, the mice belonging to groups B, C, E and F were sensitized with 1% toluene-2, 4-diisocyanate (TDI) . Five days after sensitization, TDI was painted on the ears of the mice, and delayed type hypersensitivity (DTH) was evaluated by measuring the ear thickness at 24 h later as an index. After this evaluation, the body weights of the mice, the weights of the thymus and spleen, and serum TDI-specific IgG antibody levels as an index of humoral immunity, were measured.<BR>In the mormal diet groups, the highest DTH reaction was shown in the exercise group, followed by the sedentary group. On the other hand, the DTH reactions in the SPL diet groups were significantly suppressed in both the sedentary and exercise groups. However, a slightly higher DTH reaction was shown in the exercise group than in the sedentary group. Body weights of mice in the exercise groups receiving both the normal and SPL diets were suppressed in comparison with the control and sedentary groups. Although increased spleen weights were shown in all the sensitized groups, thymus weights in the 6 groups were not changed. TDI-specific IgG antibody levels were also not changed in any of the TDI sensitized groups.<BR>From these results, the SPL diet seemed to effectively suppress the DTH reaction, and might be effective for treatment of various types of contact hypersensitivity which are currently the focus of clinical attention.

Effects of exercise and Spirulina platensis(SPL) intake on hapten specific immune response of growing mice / 体力科学

A study was performed to investigate the effects of exercise and <I>Spirulina platensis</I> (SPL) intake on the hapten specific immune response of growing mice.<BR>Male BALB/C mice aged five weeks were divided into 6 groups : Group A was a control group given a normal diet ; group B, sedentary with a normal diet ; group C, exercise with a normal diet ; group D, control with SPL diet ; group E, sedentary with a SPL diet ; group F, exercise with a SPL diet. The mice in groups C and F were trained by swimming for about 30 min 4 times a week for 5 weeks. The SPL diet was a mixture of SPL (20%) and the normal diet (80%) . At 4 weeks after the experiment, the mice belonging to groups B, C, E and F were sensitized with 1% toluene-2, 4-diisocyanate (TDI) . Five days after sensitization, TDI was painted on the ears of the mice, and delayed type hypersensitivity (DTH) was evaluated by measuring the ear thickness at 24 h later as an index. After this evaluation, the body weights of the mice, the weights of the thymus and spleen, and serum TDI-specific IgG antibody levels as an index of humoral immunity, were measured.<BR>In the mormal diet groups, the highest DTH reaction was shown in the exercise group, followed by the sedentary group. On the other hand, the DTH reactions in the SPL diet groups were significantly suppressed in both the sedentary and exercise groups. However, a slightly higher DTH reaction was shown in the exercise group than in the sedentary group. Body weights of mice in the exercise groups receiving both the normal and SPL diets were suppressed in comparison with the control and sedentary groups. Although increased spleen weights were shown in all the sensitized groups, thymus weights in the 6 groups were not changed. TDI-specific IgG antibody levels were also not changed in any of the TDI sensitized groups.<BR>From these results, the SPL diet seemed to effectively suppress the DTH reaction, and might be effective for treatment of various types of contact hypersensitivity which are currently the focus of clinical attention.