title: 1,25-dihydroxyvitamin D₃ pretreatment enhances the efficacy of allergen immunotherapy in a mouse allergic asthma model.
abstract: 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.
authors.affiliation: Institute of Respiratory Diseases, the Second Affiliated Hospital of the Third Military Medical University, Chongqing 400037, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Ma
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: Xia
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Cheng
authors.forename: Chang-Zheng
authors.initials: CZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002117:Calcitriol / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin; D002117:Calcitriol