Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Abstract

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1–5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling.

Eosinophilic Inflammation in Allergic Asthma

“…Even stress may amplify the eosinophilic infiltration in both airways and lung parenchyma among animals with allergic inflammation via immune response, demonstrating that these cells probably contribute to asthmatic response related to stress (Leick et al, 2012; Marques et al, 2012). It is well known that some modulators of the stress response have different effects on eosinophil recruitment (Nittoh et al, 1998; Machida et al, 2005), but is important to note that the complexity of these interactions still needs better clarifying.…”

“…Guinea pigs chronically exposed to OVA present an inflammatory response predominantly eosinophilic, showing a significant increase in eosinophil amount in airways, pulmonary parenchyma, and bronchoalveolar lavage (BAL), constituting an interesting experimental model to evaluate the participation of eosinophils in allergic inflammation (Tibério et al, 1997; Leick-Maldonado et al, 2004; Prado et al, 2005a,b; Lancas et al, 2006; Angeli et al, 2008; Nakashima et al, 2008; Ruiz-Schütz et al, 2009; Leick et al, 2012; Marques et al, 2012; Possa et al, 2012). …”

Different Modulators of Airways and Distal Lung Parenchyma Contractile Responses in the Physiopathology of Asthma

“…These authors also showed that the amount of these cells was reduced when the animals were treated with fluoxetine. Recently, Leick et al (129), studying the effects of stress induced by forced swimming in bronchoconstriction, observed that stress amplified the airway response to ovalbumin in guinea pigs. In addition, Marques et al (130) showed that the malefic effects of stress in asthma are related not only to the airways but to the lung distal parenchyma.…”

Inhibitory effects of 2,6-di-tert-butyl-4-hydroxymethylphenol on asthmatic responses to ovalbumin challenge in conscious guinea pigs

“…Allergens activate inflammatory cells in the airways, leading to the release of pro-inflammatory mediators, which in turn cause vascular leakage, contraction of bronchial smooth muscle, infiltration of inflammatory cells, and airway inflammation and remodeling [ 1 2 ]. Allergen provocation induces an immediate asthmatic response (IAR) that peaks at 15 to 30 min and resolves within 2 h, and a late-phase asthmatic response (LAR) that begins 4 to 12 h after allergen challenge [ 3 4 ].…”