Structural Changes in Airway Diseases: Antiremodeling Property

Monoclonal antibodies against IL-5 were shown to be effective in reducing the deposition of ECM proteins tenascin, lumican, and procollagen in the basement membrane of patients with mild asthma. In addition, anti-IL-5 reduces blood and sputum eosinophilia. Subepithelial fibrosis prevention has been observed with anti-IL-5 in a mouse model of asthma. These data suggest that these agents may influence remodeling, which might be partly preventable or reversible.
CpG: As airway inflammation in asthma is considered to be under control of Th2 lymphocytes, new therapeutic interventions that may reverse the Th2 pattern have been conceived. Bacterial DNA, precisely CpG motifs, promotes Th1 immune response in animal models. Synthesized CpG-oligonucleo-tides, known as immunostimulatory DNA sequence, are currently under study in allergic diseases. Stud-ies239,240 in murine models showed that CpG treatment reduced airway eosinophilia, IL-5, IL-4, IL-13, and GM-CSF production, and increased interferon-7 release. so

CpG oligonucleotide treatment induces a Th1 response through activation of macrophages and dendritic cells, resulting in increased IL-12 production. This leads to a higher interferon-7/IL-4 ratio, resulting in a Th1 profile. Animal studies on mouse and monkey models report a thinner subepithelial fibrosis and weaker goblet-cell hyperplasia following immunostimulatory DNA sequence treatment. Modulating Th2 toward Th1 pattern by CpG oligonucleotides therapy may possibly reduce the fibrotic process.
Anti-IgE: Treatment with anti-IgE reduces blood IgE, slightly decreases asthma symptoms and corticosteroid use, but has no effect on lung function. Treatment with anti-IgE (omalizumab) significantly reduces the airway eosinophilia in both the induced sputum, and epithelium and submucosal layers. A decrease in circulating cytokines IL-13, and IL-5 is observed with anti-IgE, while no modulation of IL-6, IL-10, and serum intracellular adhesion molecule can be detected.245 Anti-IgE presents potential antiinflammatory effects, but no antiremodeling property has been reported yet.

This entry was posted in Pulmonary Function and tagged airway inflammation, airway remodeling, antiasthmatic therapy, asthma, COPD, corticosteroids, cystic fibrosis.