Sublingual immunotherapy efficacy of Dermatophagoides farinae vaccine in a murine asthma model.

BACKGROUND: Allergen-specific sublingual immunotherapy is a potential treatment for allergic diseases. Its effective dose and underlying mechanism are still to be explored. Here, we investigated the efficacy and mechanism of sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine asthma model. METHODS: BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by sublingual treatment with Der f vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week. We analyzed their clinical symptoms, antibody levels, cytokine levels, T-cell proliferation and the regulatory T-cell numbers. RESULTS: Mice treated with high-dose Der f sublingual vaccine prior to challenge displayed alleviated symptoms such as airway hyperreactivity, lung inflammation and mucus production, as well as less eosinophilic cells in bronchoalveolar lavage fluid. Interestingly, reduced responses of Der-f-specific IgE and increased responses of Der-f-specific IgA and IgG1 were aroused in the high-dose Der f sublingual vaccine group. We also observed that interleukin-4 was reduced and interferon-gamma and interleukin-10 were increased among splenocytes and in bronchoalveolar lavage fluid, which inhibited Der-f-specific T-cell proliferation of the spleen and increased CD4+CD25+Foxp3+regulatory T cells in the spleen. However, mice treated with low-dose Der f sublingual vaccine developed allergic asthma. CONCLUSION: Our results illustrate that high-dose Der f sublingual vaccine may play a role in immunologic protection in murine allergic asthma, possibly by inducing regulatory T cells and Th1 reaction.

[Effects of erythromycin on the synthesis of interleukin-8 and gamma-glutamylcysteine synthetase induced by 4-hydroxynonenal in the bronchial epithelial cells].

OBJECTIVE: This study was to explore the role of erythromycin on the synthesis of interleukin-8 (IL-8) and gamma-GCS treated by 4-hydroxynonenal (4-HNE) in bronchial epithelial cells (16-HBE). METHOD: (1) The experiment groups were divided into 10 micromol/L 4-HNE and control groups. The phosphorylation of ERK-1, JNK, P38MAPK and the combining activity of AP-1 after 10 micromol/L 4-HNE stimulating for 0.5, 2, 4, 8, 12 hours were all estimated. (2) The IL-8 and IL-8 mRNA, gamma-GCS and gamma-GCS mRNA were measured after 4-HNE (or serum-free medium) stimulating 0.5, 2, 4, 8, 12 hours. (3) The effects of PD98059 and erythromycin on the expression of gamma-GCS, gamma-GCS mRNA, IL-8 and erythromycin on AP-1 combining activity by the 4-HNE were all detected. RESULTS: (1) The level of phosphorylation of ERK1 in the 4-HNE and control groups were 110.4+/-1.6, 114.6+/-2.4, 106.1+/-2.1, 110.2+/-2.0, 104.4+/-3.4, 112.8+/-2.4, 96.3+/-9.6, 115.4+/-3.8, 86.3+/-2.8, 113.1+/-2.6 at 0.5, 2, 4, 8, 12 hours, respectively, P<0.05. While the AP-1 combining activity in the 4-HNE and control groups were 90.6+/-2.0, 98.6+/-2.1, 85.7+/-2.2, 98.7+/-3.4, 78.2+/-2.6, 100.1+/-3.8, 70.6+/-1.8, 101.3+/-4.2, 64.9+/-4.8, 97.4+/-3.6, respectively P<0.05. (2) The level of IL-8 in the 4-HNE and control groups at 2, 4, 8, 12 hours were (87.4+/-3.8) microg/L, (63.9+/-3.8) microg/L, (98.3+/-4.2) microg/L, (65.3+/-6.2) microg/L, (102.4+/-5.7) microg/L, (64.6+/-4.8) microg/L, (116.5+/-5.6) microg/L, (63.7+/-6.6) microg/L, respectively, P<0.05. The levels of gamma-GCS at 2, 4, 8, 12 hours in two groups were 5.43+/-0.23, 4.78+/-0.26, 5.41+/-0.27, 4.03+/-0.34, 5.54+/-0.53, 3.22+/-0.31, respectively, P<0.05. IL-8 mRNA, gamma-GCS mRNA after 4-HNE stimulation were all increased compared with the control groups. (3) The expression of IL-8 and AP-1 combining activity was decreased, but synthesis of gamma-GCS was increased after treatment with PD98059 or erythromycin before treated with 4-HNE. CONCLUSION: 4-HNE could increase the expression of IL-8 in the bronchial epithelial cells, via increasing the transcribing activities of AP-1 via ERK-1 cell signal transduction ways. Erythromycin could inhibit the synthesis of IL-8 by blocking AP-1 pathway. PD98059 and erythromycin could block AP-1 transduction pathway, but increase the synthesis of gamma-GCS induced by 4-HNE in bronchial epithelial cells.

[Changes of signal transducer and transcriptional activator 5 (STAT5) in proliferative splenocytes from asthma mice induced by ovalbumin].

AIM: To investigate the changes of signal transducer and transcriptional activator 5 (STAT5) in proliferative splenocyte of asthma mice. METHODS: BALB/c mice were induced to develop asthma by intraperitoneal injection and then nebulized aspiration of OVA. The splenocytes were isolated, and the proliferation of the splenocytes was detected by MTT colorimetry. The phosphorylation of STAT5 and its location were examined by double immunohistochemical staining and the binding of STAT5 with DNA was determined by electrophoretic mobility shift assay (EMSA). RESULTS: OVA could pronouncedly induce the splenocyte proliferation of asthma mice in dose-dependent manner. Stimulation with OVA for 1 and 3 hours could lead to phosphorylation of STAT5 in splenocytes from asthma mice and increase the binding of STAT5 with DNA, suggesting that STAT5 signal pathway plays an important role in splenocyte proliferation of asthma mice induced with OVA.

[Effects of H1 blocker and inhaled corticosteroids on asthmatic patients with allergic rhinitis].

OBJECTIVE: To evaluate the therapeutic effects of H(1) blocker in combination with low dose inhaled corticosteroid on allergic asthma. METHODS: A multi-center, double blind, randomized, placebo control study was conducted in 67 patients with mild to moderate allergic asthma. Patients were randomized to receive either Loratadine 10 mg or placebo twice a day on the basis of inhaled beclomethasone dipropionate (400 microg/d for 14 days, then reduced to 200 microg/d) for 5.3 +/- 1.3 months. Symptom scores of asthma, frequencies of episode of rhinitis and common cold and doses of inhaled Salbutamol as rescue drug were recorded. Bronchial hyperresponsiveness (PD(20) FEV(1) in response to Histamine) and serum ICAM-1 and VCAM-1 were measured before and after the treatment. RESULTS: After treatment, there was much better improvement in symptom score (2.4 +/- 0.9 vs 3.1 +/- 0.9, P < 0.01), symptomatic days due to rhinitis (4.0 +/- 1.2 d/week vs 1.9 +/- 0.9 d/week, P < 0.001), episode of common cold symptom (0.8 +/- 0.5 time vs 1.1 +/- 0.4 time, P < 0.001), average doses of inhaled beta(2) agonist as rescue medication (2.6 +/- 0.9 puff/week vs 3.7 +/- 0.8 puff/week, P < 0.001) and bronchial responsiveness (P < 0.05) in Loratadine group as compared with the control group. However, there was no significant change in serum ICAM-1 and VCAM-1 levels after treatment in both groups (P > 0.05). CONCLUSIONS: On the basis of low dose inhaled corticosteroid, orally administered Loratadine significantly improves the therapeutic efficacy of asthma in patients with allergic asthma and rhinitis.