Cigarette
smoke (CS) has been identified as a predominant causative factor for
chronic obstructive pulmonary disease (
COPD), so CS-exposed rodent model of
COPD has drawn considerable interest and attention for fundamental study and
drug discovery. In the present study, using experimental
COPD model rats, the therapeutic potential of a newly prepared respirable
powder (RP) formulation of a long-acting VIP derivative, [Arg(15,20,21), Leu(17)]-VIP-GRR (
IK312532), was assessed with a focus on pro-inflammatory
biomarkers, morphological and histochemical changes, and infiltrated cells in the respiratory system. CS exposure of rats for 11 days led to the marked infiltration of inflammatory cells, except for eosinophils, in bronchiolar epithelium, followed by goblet cell
metaplasia and
hyperplasia. However, inhalation of IK312532-RP (50μg/rat) in the CS-exposed rats resulted in 74 and 71% reductions of granulocyte recruitment in bronchoalveolar lavage fluids and lung tissues, respectively, with 68% decrease of goblet cells.
Biomarker study demonstrated that the inhaled IK312532-RP could suppress the CS-evoked increase of
myeloperoxidase in both plasma and lung by 87 and 70%, respectively, possibly leading to potent suppression of neutrophilic inflammatory symptoms. The results from TUNEL staining were indicative of apoptotic damage in respiratory tissues of the CS-exposed rats, and there appeared to be marked decrease of TUNEL-positive cells in the CS-exposed rat with inhaled IK312532-RP. The present findings suggest that an inhalable formulation of
IK312532 might be efficacious as a
therapy for
COPD or other airway inflammatory diseases because of its potent immunomodulating activities.