Klier John, Fuchs Sebastian, Winter Gerhard, Gehlen Heidrun
Equine Clinic, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-University, 85764 Oberschleißheim, Germany.
Pharmaceutical Technology and Biopharmaceutics, Faculty of Chemistry and Pharmacy, Ludwig-Maximilians-University, 81377 Munich, Germany.
Animals (Basel). 2022 Aug 16;12(16):2087. doi: 10.3390/ani12162087.
Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in key clinical parameters: the arterial partial pressure of oxygen, the quantity and viscosity of tracheal mucus, and neutrophilic inflammatory cells in the respiratory tracts of the severe equine asthmatic subjects. At the immunological level, an upregulation of the regulatory antiallergic and anti-inflammatory cytokine IL-10 as well as a downregulation of the proallergic IL-4 and proinflammatory IFN-γ in the respiratory tracts of the severe equine asthmatic patients were identified in the treatment groups. CD4 T lymphocytes in the respiratory tracts of the asthmatic horses were demonstrated to downregulate the mRNA expression of Tbet and IL-8. Concentrations of matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2 were significantly decreased directly after the treatment as well as six weeks post-treatment. This innovative therapeutic concept thus opens new perspectives in the treatment of severe equine asthma and possibly also that of human asthma.
严重马哮喘是全球最常见的广泛传播的非传染性马呼吸道疾病（包括其轻度和中度形式），与接触干草粉尘和霉菌孢子有关，与人类哮喘有一定相似性，并且仍然是一个治疗难题。在多项研究中，与明胶纳米颗粒结合作为药物递送系统的免疫调节性CpG-ODN通过吸入成功施用于严重马哮喘患者。可以证明关键临床参数在一至八周内有显著、持续且不依赖变应原的改善：严重马哮喘受试者呼吸道中的动脉血氧分压、气管黏液的量和黏度以及嗜中性粒细胞炎症细胞。在免疫水平上，治疗组中严重马哮喘患者呼吸道中的调节性抗过敏和抗炎细胞因子IL-10上调，同时变应原性IL-4和促炎性IFN-γ下调。哮喘马呼吸道中的CD4 T淋巴细胞被证明可下调Tbet和IL-8的mRNA表达。治疗后以及治疗后六周，基质金属蛋白酶-2和-9以及金属蛋白酶组织抑制剂-2的浓度显著降低。因此，这种创新的治疗理念为严重马哮喘的治疗以及可能的人类哮喘治疗开辟了新的前景。
