H7N9 influenza A-induced pneumonia associated with acute myelitis in an adult.

Recently, we encountered three patients infected with an avian influenza A virus (H7N9) who exhibited upper respiratory catarrh symptoms, pharyngalgia, a high fever and hypodynamia in the early stages of the disease. Their conditions deteriorated rapidly, and one-sided pneumonia progressed to two-sided pneumonia. The patients developed respiratory failure and even acute respiratory distress syndrome (ARDS). One patient experienced numbness of the lower limbs, urinary retention and fecal incontinence. Magnetic resonance imaging (MRI) of the spinal cord indicated edema at the thoracic level, and the patient was diagnosed with acute myelitis. This report details the diagnosis and treatment of a patient with H7N9-induced pneumonia associated with acute myelitis.

[The mechanism of airway inflammation in eosinophilic bronchitis and cough variant asthma].

OBJECTIVE: To explore the characteristics of airway inflammatory cells, cytokines and inflammatory mediators in eosinophilic bronchitis (EB) and cough variant asthma (CVA) patients and to elucidate the underlying mechanism of distinct airway inflammation between EB and CVA. METHODS: This study included 15 patients with EB (EB group), 15 patients with cough variant asthma (CVA, CVA group), 14 patients with bronchial asthma (asthma group) and 14 healthy controls (healthy group). Percentage of eosinophils (EOS) in sputum induced by hypertonic saline was detected by FACS. The percentage of CD(69)(+) EOS stimulated by interleukin-5 (IL-5) and interferon γ (IFN-γ) was also detected by FACS. The expression of leukotriene C4 synthase (LTC4S) and prostaglandin-endoperoxide synthase-2 (PTGS2) mRNA in sputum was measured by real-time PCR and the concentration of leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) in sputum was measured by ELISA. RESULTS: The percentage of EOS in induced sputum was 15.8 ± 3.2 (EB group), 13.0 ± 2.7 (CVA group) and 11.6 ± 4.5 (asthma group), respectively, which were significantly higher than 1.0 ± 0.4 in the healthy group. The difference was significant and the t value was 16.31, 15.23 and 14.21 respectively (P < 0.05). After stimulated by IL-5 and IFN-γ, the percentage of CD(69)(+) EOS in induced sputum was 1.5 ± 0.4 and 1.5 ± 0.5 (EB group), 1.4 ± 0.4 and 1.4 ± 0.3 (CVA group) and 1.42 ± 0.72 and 1.37 ± 0.46 (asthma group) respectively. There was no statistical significance between these 3 groups, but when compared with 0.4 ± 0.2 and 0.4 ± 0.1 in healthy group, the difference was significant (P < 0.05). The expression of IL-5 mRNA and protein in induced sputum of EB group, CVA group and asthma group were higher than the healthy group and the difference was all statistically different (P < 0.05), but there was no statistical significance between EB group, CVA group and asthma group. The expression of IFN-γ mRNA and protein in induced sputum of each group was not different when compared with healthy group (P > 0.05). The concentration of PGE2 in induced sputum of EB group was(839 ± 69) ng/L, which was higher than (33 ± 8) ng/L of CVA group, (25 ± 6) ng/L of asthma group and (24 ± 8) ng/L of healthy group (all P < 0.01). There was no statistical difference between CVA group, asthma group and healthy group. The expression of PTGS2 in induced sputum of EB group increased significantly; when compared with CVA group, asthma group and healthy group, the difference was significant (all P < 0.01). The concentration of LTC4 in induced sputum of EB group, CVA group and asthma group was all higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA of EB group, CVA group and asthma group was also higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA and LTC4 in the EB group was higher than that in the CVA group and the asthma group (P < 0.05). The value of LTC4/PGE2 in the CVA group and the asthma group was higher than that in the EB group (t = 8.7 and 13.1, P < 0.05). CONCLUSION: These data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and CVA (or asthma) may be due to the results of differences in PGE(2) production and an imbalance between the production of bronchoconstrictor LTC(4) and bronchoprotective PGE(2) lipid mediators.

1,25-dihydroxyvitamin D3 pretreatment enhances the efficacy of allergen immunotherapy in a mouse allergic asthma model.

BACKGROUND: Allergen-specific immunotherapy can induce immune tolerance to specific allergens by regulating immune status of individuals. However, its clinical application is limited due to individual differences in efficacy among patients and un-confirmed safety. 1,25 Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has been shown to be involved in a variety of physiological processes, including immune response regulation. In the present study we explored the role of 1,25(OH)(2)D(3) pretreatment for immunotherapy. METHODS: Seventy-five BALB/c mice were randomly divided into five groups (15 mice per group). The mouse allergic asthma model was established by intra-peritoneal injection of ovalbumin (OVA, 10 µg) and aluminium hydroxide (2 mg) as an adjuvant. Intra-peritoneal injection of 50 ng of 1,25(OH)(2)D(3) served as a pretreatment, subcutaneous injection of OVA (100 µg) as an immunotherapy, and 1% OVA inhalation as a challenge. Histopathological analysis was performed on four mice per group. The number of cells and their classification in bronchoalvolar lavage (BAL) fluid were assayed. Levels of serum OVA-specific immunoglobulin E (sIgE) and IFN-γ, IL-4, IL-5 and IL-10 in BAL fluid were measured by ELISA. RESULTS: After 1,25(OH)(2)D(3) pretreatment, immunotherapy could significantly inhibit the infiltration of inflammatory cells into lung tissues and BAL fluid of mice with allergic asthma when compared with un-treated animals (eosinophils: (7.46 ± 1.34) × 10(4)/ml vs. (13.41 ± 1.67) × 10(4)/ml, P < 0.05). In addition, levels of IL-4 ((36.91 ± 7.87) pg/ml vs. (43.70 ± 6.42) pg/ml, P > 0.05) and IL-5 ((41.97 ± 7.93) pg/ml vs. (60.14 ± 8.35) pg/ml, P < 0.05) in BAL fluid and serum sIgE ((0.42 ± 0.05) vs. (0.75 ± 0.06) OD units, P < 0.05) were profoundly reduced. However, the IL-10 level in BAL fluid was significantly increased ((67.74 ± 6.57) pg/ml vs. (44.62 ± 8.81) pg/ml, P < 0.05). CONCLUSIONS: These results indicated that 1,25(OH)(2)D(3) pretreatment enhanced the inhibitory effects of immunotherapy on allergic airway inflammation. In the treatment of allergic diseases, 1,25(OH)(2)D(3) pretreatment may be beneficial for improving the efficacy of immunotherapy.

[Immunoregulatory role of 1, 25-dihydroxyvitamin D(3)-treated dendritic cells in allergic airway inflammation].

OBJECTIVE: To explore the mechanism and immunoregulatory role of 1, 25-dihydroxy vitamin D(3) [1, 25 (OH)(2)D(3)]-treated dendritic cells (DCs) in allergic airway inflammation. METHODS: Mouse bone marrow-derived DCs were treated by 1, 25 (OH)(2)D(3) for 72 h. The expression levels of different Notch ligands: Jagged1, Jagged2, Delta1, Delta3, and Delta4 in these DCs were detected by RT-PCR and Western blotting. Mouse spleen CD4+ T cells were cultured with 1, 25 (OH)(2)D(3)-treated DCs or 1, 25 (OH)(2)D(3)-treated DCs blocked by polyclonal antibody of Jagged1 or Jagged2 (control group) for 48 h. The percentage of CD4+CD25+Foxp3+ T cells in CD4+ T cells was detected by flow cytometry (FCM). Ten mice underwent intraperitoneal injection of ovalbumin (OVA) to be sensitized and then divided into 2 groups to inhale 1, 25 (OH)(2)D(3)-treated DC suspension and PBS-DC suspension respectively for 6 successive days. Then the mice were killed. Bronchoalveolar lavage fluid was obtained to detect the eosinophil count and the levels of interleukin (IL)-4, IL-6, IL-13, and interferon (IFN)-gamma, and pathological examination of lung was conducted. Spleens were taken out to isolate the CD4+ T cells, and immunolabeling and FCM were used to detect the percentage of CD4+CD25+Foxp3+ T cells. RESULTS: The mRNA and protein expression levels of Jagged1 and Jagged2 in the 1, 25 (OH)(2)D(3)-treated DCs were (0.376 +/- 0.029) and (0.786 +/- 0.034), and (0.564 +/- 0.018) and (0.632 +/- 0.026) respectively, all significantly higher than those of the control group [(0.146 +/- 0.032) and (0.124 +/- 0.025), and (0.267 +/- 0.012) and (0.098 +/- 0.012) respectively, all P < 0.01)]. The percentage of CD4+CD25+Foxp3+ T cells in the CD4+ T cells cultured with 1, 25 (OH)(2)D(3)-treated DCs was (22.49% +/- 0.56%), significantly higher than that of the a PBS control group [(6.67% +/- 0.60%), P < 0.01]. The percentage of CD4+CD25+Foxp3+ T cells in CD4+ T cells after cultured with 1, 25 (OH)(2)D(3)-treated DC blocked by polyclonal antibody of Jagged2 was (6.56% +/- 1.89%), significantly lower than that of the un-blocked control group [(20.37% +/- 1.64%), P < 0.01]. The levels of IL-4, IL-5, IL-13, and IFN-gamma, and eosinophil count in the BALF of the 1, 25 (OH)(2)D(3)-treated DC group were (33 +/- 5) pg/ml, (134 +/- 23) pg/ml, (91 +/- 11) pg/ml, and undetectable (< 12.5 pg/ml), and (236 +/- 29) x 10(3)/ml, all significantly lower than those of the PBS-DC group [(55 +/- 7) pg/ml, (332 +/- 49) pg/ml, (152 +/- 19) pg/ml, and (23 +/- 6) pg/ml, and (588 +/- 56) x 10(3)/ml, all P < 0.01]. The percentage of CD4+CD25+Foxp3+ T cells in the spleens of the 1, 25 (OH)(2)D(3)-treated DC group was (14.69% +/- 1.14%), significantly higher than that of the PBS-treated DC group [(2.38% +/- 0.14%, P < 0.01). CONCLUSION: Treatment of the DCs with 1, 25 (OH)(2)D(3) inhibits the allergic inflammation in the airway, maybe via the induction of CD4+CD25+Foxp3+ regulatory T cells by 1, 25 (OH)(2)D(3)-treated DCs through Jagged2-mediated Notch signal pathway.