neurokinin-a and Pulmonary-Disease--Chronic-Obstructive

The tachykinins substance P and neurokinin A are present in human airways, in sensory nerves and immune cells. Tachykinins can be recovered from the airways after inhalation of ozone, cigarette smoke or allergen. They interact in the airways with tachykinin NK1, NK2 and NK3 receptors to cause bronchoconstriction, plasma protein extravasation, and mucus secretion and to attract and activate immune cells. In preclinical studies they have been implicated in the pathophysiology of asthma and chronic obstructive pulmonary disease, including allergen- and cigarette smoke induced airway inflammation and bronchial hyperresponsiveness and mucus secretion. Dual NK1/NK2 or triple NK1/NK2/NK3 tachykinin receptor antagonists offer therapeutic potential in airway diseases such as asthma and chronic obstructive pulmonary disease.

Topics: Animals; Asthma; Bronchoconstriction; Clinical Trials as Topic; Disease Models, Animal; Humans; Neurokinin A; Neurons, Afferent; Neurotransmitter Agents; Pulmonary Disease, Chronic Obstructive; Receptors, Tachykinin; Respiratory System; Respiratory System Agents; Substance P

Involvement of tachykinins in airway inflammation has been demonstrated in animal models, but evidence in humans is sparse. The aim of this study was to quantify the levels of substance P and neurokinin A in induced sputum of patients with chronic obstructive pulmonary disease (COPD) and to compare them with the levels in smokers with normal lung function and healthy nonsmokers. Content of tackykinins was measured in 12 sputum samples collected during stable condition and nine sputum samples collected during exacerbations from 13 COPD patients, in eight sputum samples from smokers with normal lung function and in nine from healthy nonsmokers. Patients with COPD exacerbations had a lower sputum content of substance P compared with the other 3 groups (p<0.05). No differences were found between patients with stable COPD, smokers with normal lung function, and nonsmokers. Sputum levels of neurokinin A were trending in the same direction of substance P, but the significant difference was reached for the paired sputum samples collected from the same COPD patients (n=8) during exacerbation and in stable condition. COPD exacerbations are associated with a reduced sputum content of substance P and neurokinin A. These tackykinins might be involved in COPD exacerbations.

Topics: Aged; Female; Humans; Male; Middle Aged; Neurokinin A; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Smoking; Sputum; Substance P

N-Acetylcysteine (NAC) reduces the risk of exacerbation of chronic obstructive pulmonary disease (COPD). Although NAC also has anti-inflammatory activity, the detailed mechanism leading to its protective role remains to be elucidated. We tested the impact of NAC against the effects of lipopolysaccharide (LPS) in an ex vivo model of COPD exacerbation, and investigated the role of neurokinin A (NKA) in this context.. Isolated airways from COPD patients were incubated overnight with LPS (100 ng/ml). NAC was tested at concentrations resembling the plasma levels elicited by oral administration of NAC at 200 mg/day (very low dose), 600 mg/day (low dose) and 1.200 mg/day (high dose).. NAC at high concentrations normalized the peroxidase activity, H. This study demonstrates that, along with its well-known antioxidant activity, the protective effect of NAC against the detrimental effect of LPS is due to the modulation of NKA and IL-6 levels.

Topics: Acetylcysteine; Biological Availability; Bronchi; Disease Progression; Female; Humans; Inflammation; Lipopolysaccharides; Male; Middle Aged; Models, Biological; Neurokinin A; Oxidative Stress; Protective Agents; Pulmonary Disease, Chronic Obstructive; Regression Analysis