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Objectives: Inhalation of immunostimulatory bacterial DNA segments (cytosine-phosphate-guanosine-oligodeoxynucleotides, CpG-
ODN) has been shown to normalize clinical and cytologic parameters in severe equine asthma (recurrent airway obstruction, RAO). We hypothesized that CpG-ODN inhalation reduces the misbalance of elastinolytic activity in horses affected by RAO.
Methods: 20 horses diagnosed as RAO by clinical examinations using a scoring system were included. All horses were treated with inhalative CpG-ODN for 14 days in 2-day intervals. Matrix-metalloproteinase (MMP-2/-9) and tissue inhibitors of metalloproteinases (TIMP-1/-2) concentrations were measured in tracheal aspirates using equine ELISA kits (USCN Life Science Inc.) before, immediately and 6 weeks after CpG-ODN inhalation.
Results: MMP and TIMP concentrations correlated with the results of clinical scoring in all stages of equine asthma. Inhalation therapy led
to significant reductions in clinical scores. MMP-2, MMP-9 and TIMP-2 concentrations were reduced significantly immediately, and all MMP and TIMP concentrations 6 weeks after therapy.
Discussion: In equine asthma, overexpression of MMPs contributes to pathological tissue destruction, while TIMPs counteract MMPs with
overexpression leading to fibrosis formation. The results of this study show that CpG-ODN inhalation is an effective therapy to address a misbalance in equine asthma.
Conclusions: Misbalance of elastinolytic activity was positively influenced by CpG-ODN inhalation for at least 6 post therapy, which may reduce the remodeling of the extracellular matrix. Further studies should evaluate this effect in comparison to glucocorticoid inhalation therapy.
Significance: CpG-ODN inhalation may be an effective therapy in prevention of pulmonary fibrosis formation in equine asthma.