Effects of corticosteroid, montelukast and iNOS inhibition on distal lung with chronic inflammation

We evaluated the effects of anti-iNOS (1400W – W) associated with leukotriene antagonist (montelukast – M) or corticosteroid (dexamethasone – D) on distal lung of guinea pigs (GP) with chronic pulmonary inflammation.MethodsGP were inhaled with ovalbumin (OVA-2×/week/4 weeks), treated with M (OVAM), D (OVAD) and/or W (OVAW, OVADW, OVAMW) and distal lungs were evaluated by morphometry.ResultsIsolated treatments were not sufficient to reduce all parameters. In OVADW, all parameters were reduced with greater reduction in elastic fibers, TIMP-1, IL-4, IL-5, IFN-gamma and PGF2-alpha compared with OVAD (p < 0.05). OVAMW potentiated the reduction of actin, elastic fibers, TIMP-1, IL-4, IL-5, TGF-beta, IFN-gamma, iNOS, and PGF2-alpha to a greater extent than OVAM (p < 0.05). A reduction of TIMP-1, IL-4, IL-5, TGF-beta, IFN-gamma and iNOS was observed in OVADW compared with OVAMW (p < 0.05).ConclusionsAlthough anti-iNOS paired with montelukast or dexamethasone yields better results than isolated treatments, the most effective pairing for controlling inflammation, oxidative stress and remodeling in this asthma model was found to be corticosteroids and anti-iNOS.

► Distal lung inflammation was reduced by iNOS inhibitor and corticosteroids. ► Matrix remodeling was reverted by iNOS inhibitor and corticosteroids. ► Distal lung inflammation was reduced by iNOS inhibitor and montelukast. ► Matrix remodeling was reverted by iNOS inhibitor and montelukast. ► iNOS inhibitor and corticosteroids or montelukast better controls oxidative stress.