Serebrisky D, Teper A A, Huang C K, Lee S Y, Zhang T F, Schofield B H, Kattan M, Sampson H A, Li X M
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Immunol. 2000 Nov 15;165(10):5906-12. doi: 10.4049/jimmunol.165.10.5906.
CpG oligodeoxynucleotides (CpG-ODN) administered during Ag sensitization or before Ag challenge can inhibit allergic pulmonary inflammation and airway hyperreactivity in murine models of asthma. In this study, we investigated whether CpG-ODN can reverse an ongoing allergic pulmonary reaction in a mouse model of asthma. AKR mice were sensitized with conalbumin followed by two intratracheal challenges at weekly intervals. CpG-ODN was administered 24 h after the first Ag challenge. CpG-ODN administration reduced Ag-specific IgE levels, bronchoalveolar lavage fluid eosinophils, mucus production, and airway hyperreactivity. We found that postchallenge CpG-ODN treatment significantly increased IFN-gamma concentrations and decreased IL-13, IL-4, and IL-5 concentrations in bronchoalveolar lavage fluids and spleen cell culture supernatants. Postchallenge CpG-ODN treatment also increased B7.1 mRNA expression and decreased B7.2 mRNA expression in lung tissues. These results suggest that CpG-ODN may have potential for treatment of allergic asthma by suppressing Th2 responses during IgE-dependent allergic airway reactions. The down-regulation of Th2 responses by CPG-ODN may be associated with regulation of the costimulatory factors B7.1 and B7.2.
在抗原致敏期间或抗原激发前给予的CpG寡脱氧核苷酸(CpG-ODN)可抑制哮喘小鼠模型中的过敏性肺部炎症和气道高反应性。在本研究中,我们调查了CpG-ODN是否能逆转哮喘小鼠模型中正在进行的过敏性肺部反应。用伴清蛋白致敏AKR小鼠,随后每周进行两次气管内激发。在首次抗原激发后24小时给予CpG-ODN。给予CpG-ODN可降低抗原特异性IgE水平、支气管肺泡灌洗液嗜酸性粒细胞、黏液分泌和气道高反应性。我们发现激发后给予CpG-ODN治疗可显著提高支气管肺泡灌洗液和脾细胞培养上清液中IFN-γ的浓度,并降低IL-13、IL-4和IL-5的浓度。激发后给予CpG-ODN治疗还可增加肺组织中B7.1 mRNA的表达并降低B7.2 mRNA的表达。这些结果表明,CpG-ODN可能通过在IgE依赖性过敏性气道反应期间抑制Th2反应而具有治疗过敏性哮喘的潜力。CPG-ODN对Th2反应的下调可能与共刺激因子B7.1和B7.2的调节有关。