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Chronic obstructive pulmonary disease (COPD) is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti-interleukin (IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE + PREVENTIVE ANTI-IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI-IL-17 (ET). On the 29th day, animals were anesthetized with thiopental, tracheotomized, and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti-IL-17 decreased respiratory resistance and elastance, airway resistance, elastance of pulmonary parenchyma, eNO, and Lm compared with EC. There was reduction in total cells and macrophages in ET compared with EC. Both treatments decreased nuclear factor-кB, inducible nitric oxide synthase, matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor-β, tumor necrosis factor-α, neutrophils, IL-1β, isoprostane, and IL-17 in airways and alveolar septa; collagen fibers, decorin and lumican in airways; and elastic fibers and fibronectin in alveolar septa compared with EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP and a reduction of eNO synthase in airways in ET. In conclusion, both treatments with anti-IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.

Background . The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and acute lung damage is well known. However, the mechanism involved in the effects of repeated exposures of PM in the lung injury is poorly documented. This study tested the hypotheses that chronic nasal instillation of residual oil fly ash (ROFA) induced not only distal lung and airway inflammation but also remodeling. In addition, we evaluated the effects of inducible nitric oxide inhibition in these responses. For this purpose, airway and lung parenchyma were evaluated by quantitative analysis of collagen and elastic fibers, immunohistochemistry for macrophages, neutrophils, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and alveolar septa 8-iso prostaglandin F2 α (8-iso-PGF-2 α ) detection. Anesthetized i n vivo (airway resistance, elastance, H, G, and Raw) respiratory mechanics were also analyzed. C57BL6 mice received daily 60ul of ROFA (intranasal) for five (ROFA-5d) or fifteen days (ROFA-15d). Controls have received saline (SAL). Part of the animals has received 1400W (SAL+1400W and ROFA-15d+1400W), an iNOS inhibitor, for four days before the end of the protocol. A marked neutrophil and macrophage infiltration and an increase in the iNOS, nNOS, and 8-iso-PGF2 α expression was observed in peribronchiolar and alveolar wall both in ROFA-5d and in ROFA-15d groups. There was an increment of the collagen and elastic fibers in alveolar and airway walls in ROFA-15d group. The iNOS inhibition reduced all alterations induced by ROFA, except for the 8-iso-PGF2 α expression. In conclusion, repeated particulate matter exposures induce extracellular matrix remodeling of airway and alveolar walls, which could contribute to the pulmonary mechanical changes observed. The mechanism involved is, at least, dependent on the inducible nitric oxide activation.

Protease/anti-protease imbalance is the main pathogenic mechanism of emphysema and protease inhibitors have been recognized as potential molecules to treat the disease conditions. In this work the rBmTI-6 first domain (rBmTI-6-D1), a recombinant Kunitz-type serine proteinase inhibitor, was used to verify its effect in prevention or minimization of PPE-induced emphysema in mice. C57BL/6 mice were submitted to a PPE-induced emphysema model and treated with rBmTI-6-D1 before the emphysema development. We showed that the rBmTI-6-D1 treatment was sufficient to avoid the loss of elastic recoil, an effective decrease in alveolar enlargement and in the number of macrophages and lymphocytes in bronchoalveolar lavage fluid. Proteolytic analysis showed a significant increase in elastase activity in PPE-VE (induced emphysema) group that is controlled by rBmTI-6-D1. Kallikrein activity was decreased in the PPE-rBmTI6 (induced emphysema and inhibitor treated) group when compared to PPE-VE group. Although rBmTI-6-D1, did not present a neutrophil elastase (NE) inhibitory activity, the results show that the inhibitor interfered in the pathway of NE secretion in PPE-emphysema mice model. The role of rBmTI-6-D1 in the prevention of emphysema development in the mice model, apparently, is related with a control of inflammatory response due the trypsin/kallikrein inhibitory activity of rBmTI-6-D1., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Lung volume reduction surgery (LVRS) is an option for emphysematous patients who are awaiting lung transplantation. LVRS reduces nonfunctional portions of lung tissues and favors the compensatory lung growth (CLG) of the remaining lobes. This phenomenon diminishes dyspnea and improves both the respiratory mechanics and quality of life for the patients. An animal model of elastase-induced pulmonary emphysema was used to investigate the structural and functional lung response after LVRS. Bilobectomy was performed six weeks after elastase instillation. Two weeks after bilobectomy, CLG effects were evaluated by lung mechanics and histomorphometric analysis. After bilobectomy, the emphysematous animals presented decreased mean linear intercepts, increased elastic fiber proportion, and increased alveolar surface density, total volumes of airspace, tissue and respiratory region and absolute surface area. We conclude that bilobectomy promoted CLG in emphysematous animals, resulting in alveolar architecture repair.

Background: Creatine (Cr) is a dietary supplement that presents beneficial effects in experimental models of heart and brain ischemia and reperfusion (I/R) injury. It can improve adenosine 5'-triphosphate generation and reduce cell damage. This study evaluated the effects of Cr supplementation in a model of lung I/R., Methods: Forty male Wistar rats were divided into 4 groups: sham operated, Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response., Results: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p < 0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar lavage fluid and in the systemic circulation (p < 0.001). The levels of interleukin-1β (p < 0.05), tissue damping, and tissue elastance (p < 0.05) were also minimized. Cr also inhibited pulmonary edema formation (total proteins in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001) and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05), reduced expression of Toll-like receptor (TLR) 4, and increased expression of TLR7 in lung tissue (p < 0.001)., Conclusions: Cr supplementation presents pulmonary and systemic protective effects in acute lung injury induced by I/R in rats. These beneficial effects seem to be related to the anti-inflammatory and anti-oxidant properties of Cr and modulation of TLRs., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Studies suggest that airborne pollutants are important cofactors in the exacerbation of lung diseases. The role of DC on the exacerbation of lung inflammation induced by particulate matter pollutants is unclear. We evaluated the effects of residual oil fly ash (ROFA) on the phenotype and function of bone marrow-derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. In a model of asthma, exposure to ROFA exacerbated pulmonary inflammation, which was attributed to the increase of eosinophils, IL-5- and IFN-γ-producing T cells, and goblet cells as well as decreased number of Treg and pDC. However, the ROFA showed no ability to modulate the production of anaphylactic IgE. In vitro studies showed that ROFA directly induced the maturation of DCs up-regulating the expression of co-stimulatory molecules and cytokines and MMP production in an uptake-dependent and oxidative stress-dependent manner. Furthermore, ROFA-pulsed BMDC transferred to allergic mice exacerbated eosinophilic inflammation as well as promoted increased epithelial and goblet cells changes. Thus, pollutants may constitute an important and risk factor in the exacerbation of asthma with inhibition of the negative regulatory signals in the lung, with enhanced mDC activation that sustains the recruitment of effector T lymphocytes and eosinophil., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Unlabelled: 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., Methods: GP 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., Results: Isolated 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)., Conclusions: Although 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., (Copyright © 2012. Published by Elsevier B.V.)

Aims: Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation., Methods: GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation., Results: Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF- κ B, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF- κ B positive cells than Montelukast (P < 0.05)., Conclusions: In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response.

The effect of Bacillus Calmette-Guérin (BCG) treatment in allergic pulmonary reaction was studied in mice genetically selected accordingly to a High (H-IVA) or Low (L-IVA) antibody responsiveness. Mice were immunized with ovalbumin (OVA) or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE and IgG1 anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar lavage and the compliance and conductance of respiratory system were evaluated. H-IVA mice were found more susceptible than L-IVA, and BCG was able to inhibit simultaneously the production of IgE, the bronchopulmonary inflammation and bronchial hyperresponsiveness in these genetically selected mice.

Objective: We examined whether mechanical ventilation with low tidal volume induces polymorphonuclear infiltration and proinflammatory and profibrogenic responses in rat lungs compared dependent and nondependent lung region to expression of interleukin-1beta (IL-1beta) and alpha-1 procollagen III (PC III) mRNA., Design: An experimental, randomized and controlled protocol with previously normal rats., Interventions: Three groups of ten animals were studied. Two groups were ventilated (FIO2=0.3) in supine position for 1 h without positive end expiratory pressure, one group with a low tidal volume (6 ml/kg), and the other with a high tidal volume (24 ml/kg). In the third group animals were kept in spontaneous ventilation for 1 h., Measurements and Results: After ventilation the right lung was used to quantify polymorphonuclear infiltration. The left lung was divided into dependent and nondependent regions, and expression of IL-1beta and PC III mRNA was quantified by northern blot analysis. The group ventilated with low tidal volume had greater polymorphonuclear infiltration IL-1beta and PC III mRNA expression than the nonventilated group. Similar results were observed with high tidal volumes. There was no difference between low and high tidal volume ventilation. Expression levels of IL-1beta and PC III mRNA were higher in the nondependent region of ventilated groups and equal in the nonventilated group., Conclusions: Even a low tidal volume mode of mechanical ventilation induces proinflammatory and profibrogenic response, with a nondependent predominance for IL-1beta and PC III mRNA expression in supine, ventilated, previously normal rats.