The Anti-Inflammatory Peptide P Is a Candidate Molecule for Asthma Treatment.

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the P family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether P could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving P at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with P showed no airway hyperreactivity or lung remodeling. P acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, P prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed P as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.