In the present study the effects of
bradykinin receptor antagonists were investigated in a murine model of
asthma using BALB/c mice immunized with
ovalbumin/alum and challenged twice with aerosolized
ovalbumin. Twenty four hours later eosinophil proliferation in the bone marrow, activation (lipid bodies formation), migration to lung parenchyma and airways and the contents of the pro-angiogenic and pro-fibrotic
cytokines TGF-beta and
VEGF were determined. The antagonists of the constitutive
B(2) (
HOE 140) and inducible B(1) (R954) receptors were administered intraperitoneally 30min before each challenge. In sensitized mice, the
antigen challenge induced eosinophil proliferation in the bone marrow, their migration into the lungs and increased the number of lipid bodies in these cells. These events were reduced by treatment of the mice with the B(1) receptor antagonist. The
B(2) antagonist increased the number of eosinophils and lipid bodies in the airways without affecting eosinophil counts in the other compartments. After challenge the airway levels of
VEGF and
TGF-beta significantly increased and the B(1) receptor antagonist caused a further increase. By immunohistochemistry techniques
TGF-beta was found to be expressed in the muscular layer of small blood vessels and
VEGF in bronchial epithelial cells. The B(1) receptors were expressed in the endothelial cells. These results showed that in a murine model of
asthma the B(1) receptor antagonist has an inhibitory effect on eosinophils in selected compartments and increases the production of
cytokines involved in tissue repair. It remains to be determined whether this effects of the B(1) antagonist would modify the progression of the allergic
inflammation towards resolution or rather towards
fibrosis.