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Background: Aerobic exercise decreases pulmonary inflammation and remodeling in experimental models of allergic asthma. However, the effects of aerobic exercise on pulmonary inflammation of nonallergic origin, such as in experimental models of acute lung injury induced by lipopolysaccharide (LPS), have not been evaluated. Objective: The present study evaluated the effects of aerobic exercise in a model of LPS-induced acute lung injury. Methods: BALB/c mice were divided into four groups: Control, Aerobic Exercise, LPS, and Aerobic Exercise + LPS. Swimming tests were conducted at baseline and at 3 and 6 wk. Low-intensity swimming training was performed for 6 wk, four times per week, 60 min per session. Intranasal LPS (1 mg[middle dot]kg-1 (60 [mu]g per mouse)) was instilled 24 h after the last swimming physical test in the LPS and Aerobic Exercise + LPS mice, and the animals were studied 24 h after LPS instillation. Exhaled nitric oxide, respiratory mechanics, total and differential cell counts in bronchoalveolar lavage, and lung parenchymal inflammation and remodeling were evaluated. Results: LPS instillation resulted in increased levels of exhaled nitric oxide (P < 0.001), higher numbers of neutrophils in the bronchoalveolar lavage (P < 0.001) and in the lung parenchyma (P < 0.001), and decreased lung tissue resistance (P < 0.05) and volume proportion of elastic fibers (P < 0.01) compared with the Control group. Swim training in LPS-instilled animals resulted in significantly lower exhaled nitric oxide levels (P < 0.001) and fewer neutrophils in the bronchoalveolar lavage (P < 0.001) and the lung parenchyma (P < 0.01) compared with the LPS group. Conclusions: These results suggest that low-intensity swimming training inhibits lung neutrophilic inflammation, but not remodeling and impaired lung mechanics, in a model of LPS-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50 µl, 0.667 IU) to induce emphysema. Treatment with PNU-282987 (2.0 mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1β, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The pathway that links good communication skills and better health outcomes is still unclear. However, it is known that the way that physicians and patients communicate with each other has direct consequences on more "proximal outcomes", such as perceptions of physician empathy and patient satisfaction. However, which specific communication skills lead to those patient outcomes is still unknown. In this study, the authors aimed to analyze which specific patient and physician communication skills are correlated to patients' satisfaction with care and patient-perceived physician empathy., Methods: The authors classified and quantified verbal and nonverbal communication of second-year internal medicine residents and their patients through video recordings of their consultations. Patients also rated their satisfaction with care and the physician's empathy for them., Results: Using a linear regression model, the authors identified that patients' and physicians' expressions of disapproval, physicians' disruptions, and patients' use of content questions negatively correlated to patients' satisfaction and patient-perceived physician empathy. Conversely, patient affective behaviors and the physician's provision of advice/suggestion were positively correlated to at least one of the patient-measured outcomes., Conclusion: Our findings point to the importance of physicians' attentiveness to patients' communication cues. Training physicians to interpret those cues could help develop more satisfactory and empathic therapeutic relationships., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Prolonged exposure to iron powder and other mineral dusts can threaten the health of individuals, especially those with COPD. The goal of this study was to determine how environmental exposure to metal dust from two different mining centers in Brazil affects lung mechanics, inflammation, remodeling and oxidative stress responses in healthy and elastase-exposed mice. This study divided 72 male C57Bl/6 mice into two groups, the summer group and the winter group. These groups were further divided into six groups: control, nonexposed (SAL); nonexposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, macrophage iron and alveolar wall alterations (mean linear intercept-Lm). The Lm was increased in the ELA, ELA-L1 and ELA-L2 groups compared to the SAL group (p < 0.05). There was an increase in the total number of cells and macrophages in the ELA-L1 and ELA-L2 groups compared to the other groups (p < 0.05). Compared to the ELA and SAL groups, the exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) exhibited increased expression of IL-1β, IL-6, IL-10, IL-17, TNF-α, neutrophil elastase, TIMP-1, MMP-9, MMP-12, TGF-β, collagen fibers, MUC5AC, iNOS, Gp91phox, NFkB and iron positive macrophages (p < 0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between inflammation remodeling, oxidative stress and NFkB with elastance, resistance of lung tissue and iron positive macrophages (p < 0.05). Environmental exposure to iron, confirmed by evaluation of iron in alveolar macrophages and in air, exacerbated inflammation, initiated remodeling, and induced oxidative stress responses in exposed mice with and without emphysema. Activation of the iNOS, Gp91phox and NFkB pathways play a role in these changes., (© 2024. The Author(s).)

Lung inflammation is modulated by cholinergic signaling and exercise training protects mice against pulmonary emphysema development; however, whether exercise training engages cholinergic signaling is unknown., Aims: As cholinergic signaling is directly linked to the vesicular acetylcholine transporter (VAChT) levels, we evaluated whether the effects of aerobic exercise training depend on the VAChT levels in mice with pulmonary emphysema., Main Methods: Wild-type (WT) and mutant (KD HOM ) mice (65-70% of reduction in VAChT levels) were exposed to cigarette smoke (30 min, 2×/day, 5×/week, 12 weeks) and submitted or not to aerobic exercise training on a treadmill (60 min/day, 5×/week, 12 weeks). Lung function and inflammation were evaluated., Key Findings: Cigarette smoke reduced body mass in mice (p < 0.001) and increased alveolar diameter (p < 0.001), inflammation (p < 0.001) and collagen deposition (p < 0.01) in lung tissue. Both trained groups improved their performance in the final physical test compared to the initial test (p < 0.001). In WT mice, exercise training protected against emphysema development (p < 0.05), reduced mononuclear cells infiltrate (p < 0.001) and increased MAC-2 positive cells in lung parenchyma (p < 0.05); however, these effects were not observed in KD HOM mice. The exercise training reduced iNOS-positive cells (p < 0.001) and collagen fibers deposition (p < 0.05) in lung parenchyma of WT and KD HOM mice, although KD HOM mice showed higher levels of iNOS-positive cells., Significance: Our data suggest that the protective effects of aerobic exercise training on pulmonary emphysema are, at least in part, dependent on the integrity of the lung cholinergic signaling., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Air pollution has been identified as one of the main environmental risks to health. Since exercise training seems to act as an anti-inflammatory modulator, our hypothesis is that exercise training prevents damage to respiratory and cardiovascular function caused by diesel exhaust particle (DEP) exposure. This study aimed to evaluate whether aerobic exercise training prior to DEP exposure prevents inflammatory processes in the pulmonary and cardiovascular systems. Therefore, BALB/C male mice were or were not submitted to a 10-week exercise training protocol (5×/week, 1 h/d), and after four weeks, they were exposed to DEP in a chamber with 24 μg/m 3 PM2.5 or filtered air. Heart rate variability, lung mechanics and bronchoalveolar lavage fluid, cytokines and polymorphonuclear cells in the lung parenchyma were evaluated. Exposure to DEPs reduced heart rate variability and the elastance of the respiratory system and increased the number of cells in bronchoalveolar lavage fluid, as well as macrophages, neutrophils and lymphocytes, the density of polymorphonuclear cells and the proportion of collagen fibres in the lung parenchyma. Additionally, DEP-exposed animals showed increased expression of IL-23 and IL-12p40 (proinflammatory cytokines) and inducible nitric oxide synthase. Exercise training avoided the increases in all these inflammatory parameters, except the elastance of the respiratory system, the amount of collagen fibres and the expression of inducible nitric oxide synthase. Additionally, trained animals showed increased expression of the anti-inflammatory cytokine IL-1ra. Although our data showed a reduction in proinflammatory markers and an increase in markers of the anti-inflammatory pathway, these changes were not sufficient to prevent damage to the lung and cardiovascular function induced by DEPs. Based on these data, we propose that aerobic exercise training prevents the lung inflammatory process induced by DEPs, although it was not sufficient to avoid chronic damage, such as a loss of lung function or cardiovascular events., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the clinical evolution, functional parameters and inflammatory activity of asthma in patients who submitted to an educational intervention. 58 adult patients over 18 years of age with partly controlled and uncontrolled asthma were randomized into an intervention group (IG) (N = 32) and a control group (CG) (N = 26) and evaluated for 12 weeks. The Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Asthma Quality Life Questionnaire (AQLQ) and Beck Depression Inventory (BDI) questionnaires were applied. Spirometry, exhaled nitric oxide (NO), exhaled breath condensate (EBC) and induced sputum (IS), measurement of the peak flow and symptoms were performed. The IG patients received an educational activity for 30 min applied by a nurse. Statistical analysis: analysis of variance with repeated intragroup measures. IG presented a decreased number of eosinophils in IS and IL-17A in EBC, an increase in the percentage of FEV 1 before and after bronchodilator and an improvement in quality of life compared to the CG. There was an improvement in depression levels and a decrease in IL-4 and IL-5 in the IS and in the EBC in both groups. Our results suggest that an educational intervention can bring benefits concerning the control of inflammation, lung function alterations, quality of life and levels of depression in asthmatic patients. Registration: ClinicalTrials.gov; NCT03655392., (© 2021. The Author(s).)

Acute lung injury (ALI) is an important public health problem. The present work investigated whether dehydrodieugenol B treatment, a compound isolated from Brazilian plant Nectandra leucantha (Lauraceae), modulates experimental ALI and compared the observed effects to eugenol. Effects of dehydrodieugenol B in vitro in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were evaluated. The lung and systemic inflammatory profile, lung function, and possible mechanisms involved in BALB/C male mice (6-8 weeks) with ALI induced by LPS instillation (5 mg/kg) was assayed. Dehydrodieugenol B did not affect the cell viability and inhibited the increase in NO release and IL-1β and IL-6 gene expression induced by LPS. In vivo , both compounds reduced lung edema, inflammatory cells, and the IL-6 and IL-1 β levels in bronchoalveolar lavage fluid, as well as reduced inflammatory cell infiltration and those positive to iNOS, MMP-9, and TIMP-1, and reduced the collagen content and the 8-isoprostane expression in lung tissue. Eugenol and dehydrodieugenol B also inhibited the phosphorylation of Jc-Jun-NH2 terminal Kinase (JNK), a signaling protein involved in the MAPKinase pathway. There was no effect of these compounds in lung function. Therefore, eugenol and dehydrodieugenol B ameliorates several features of experimental ALI and could be considered as a pharmacological tool to ameliorate acute lung inflammation.

Acetylcholine (ACh), the neurotransmitter of the cholinergic system, regulates inflammation in several diseases including pulmonary diseases. ACh is also involved in a non-neuronal mechanism that modulates the innate immune response. Because inflammation and release of pro-inflammatory cytokines are involved in pulmonary emphysema, we hypothesized that vesicular acetylcholine transport protein (VAChT) deficiency, which leads to reduction in ACh release, can modulate lung inflammation in an experimental model of emphysema. Mice with genetical reduced expression of VAChT (VAChT KD HOM 70%) and wild-type mice (WT) received nasal instillation of 50 uL of porcine pancreatic elastase (PPE) or saline on day 0. Twenty-eight days after, animals were evaluated. Elastase instilled VAChT KD HOM mice presented an increase in macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid and MAC2-positive macrophages in lung tissue and peribronchovascular area that was comparable to that observed in WT mice. Conversely, elastase instilled VAChT KD HOM mice showed significantly larger number of NF-κB-positive cells and isoprostane staining in the peribronchovascular area when compared to elastase-instilled WT-mice. Moreover, elastase-instilled VAChT-deficient mice showed increased MCP-1 levels in the lungs. Other cytokines, extracellular matrix remodeling, alveolar enlargement, and lung function were not worse in elastase-instilled VAChT deficiency than in elastase-instilled WT-controls. These data suggest that decreased VAChT expression may contribute to the pathogenesis of emphysema, at least in part, through NF-κB activation, MCP-1, and oxidative stress pathways. This study highlights novel pathways involved in lung inflammation that may contribute to the development of chronic obstrutive lung disease (COPD) in cholinergic deficient individuals such as Alzheimer's disease patients., (© 2021. The Author(s).)

In the present work, the anti-inflammatory and antiasthmatic potential of biseugenol, isolated as the main component from n -hexane extract from leaves of Nectandra leucantha and chemically prepared using oxidative coupling from eugenol, was evaluated in an experimental model of mixed-granulocytic asthma. Initially, in silico studies of biseugenol showed good predictions for drug-likeness, with adherence to Lipinski's rules of five (RO5), good Absorption, Distribution, Metabolism and Excretion (ADME) properties and no alerts for Pan-Assay Interference Compounds (PAINS), indicating adequate adherence to perform in vivo assays. Biseugenol (20 mg·kg -1 ) was thus administered intraperitoneally (four days of treatment) and resulted in a significant reduction in both eosinophils and neutrophils of bronchoalveolar lavage fluid in ovalbumin-sensitized mice with no statistical difference from dexamethasone (5 mg·kg -1 ). As for lung function parameters, biseugenol (20 mg·kg -1 ) significantly reduced airway and tissue damping in comparison to ovalbumin group, with similar efficacy to positive control dexamethasone. Airway hyperresponsiveness to intravenous methacholine was reduced with biseugenol but was inferior to dexamethasone in higher doses. In conclusion, biseugenol displayed antiasthmatic effects, as observed through the reduction of inflammation and airway hyperresponsiveness, with similar effects to dexamethasone, on mixed-granulocytic ovalbumin-sensitized mice.

Background: Eugenol, a common phenylpropanoid derivative found in different plant species, has well-described anti-inflammatory effects associated with the development of occupational hypersensitive asthma. Dehydrodieugenol, a dimeric eugenol derivative, exhibits anti-inflammatory and antioxidant activities and can be found in the Brazilian plant species Nectandra leucantha (Lauraceae). The biological effects of dehydrodieugenol on lung inflammation remain unclear., Purpose: This study aimed to investigate the effects of eugenol and dehydrodieugenol isolated from N. leucantha in an experimental model of asthma., Methods: In the present work, the toxic effects of eugenol and dehydrodieugenol on RAW 264.7 cells and their oxidant and inflammatory effects before lipopolysaccharide (LPS) exposure were tested. Then, male BALB/c mice were sensitized with ovalbumin through a 29-day protocol and treated with vehicle, eugenol, dehydrodieugenol or dexamethasone for eight days beginning on the 22nd day until the end of the protocol. Lung function; the inflammatory profile; and the protein expression of ERK1/2, JNK, p38, VAChT, STAT3, and SOCS3 in the lung were evaluated by immunoblotting., Results: Eugenol and dehydrodieugenol were nontoxic to cells. Both compounds inhibited NO release and the gene expression of IL-1β and IL-6 in LPS-stimulated RAW 264.7 cells. In OVA-sensitized animals, dehydrodieugenol reduced lung inflammatory cell numbers and the lung concentrations of IL-4, IL-13, IL-17, and IL-10. These anti-inflammatory effects were associated with inhibition of the JNK, p38 and ERK1/2, VAChT and STAT3/SOCS3 pathways. Moreover, treatment with dehydrodieugenol effectively attenuated airway hyperresponsiveness., Conclusion: The obtained data demonstrate, for the first time, that dehydrodieugenol was more effective than eugenol in counteracting allergic airway inflammation in mice, especially its inhibition of the JNK, p38 and ERK1/2, components of MAPK pathway. Therefore, dehydrodieugenol can be considered a prototype for the development of new and effective agents for the treatment of asthmatic patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cigarette smoke (CS) exposure reduces skeletal muscle function; however, the mechanisms involved have been poorly investigated. The current study evaluated the temporal effects of aerobic exercise training on oxidant and antioxidant systems as well as inflammatory markers in skeletal muscle of mice exposed to CS. Mice were randomly allocated to control, exercise, smoke, and smoke+exercise groups and 3 time points (4, 8, and 12 weeks; n = 12 per group). Exercise training and CS exposure were performed for 30 min/day, twice a day, 5 days/week for 4, 8, and 12 weeks. Aerobic exercise improved functional capacity and attenuated the increase in the cachexia index induced by CS exposure after 12 weeks. Concomitantly, exercise training downregulated tumor necrosis factor α concentration, glutathione oxidation, and messenger RNA (mRNA) expression of Keap1 ( P < 0.01) and upregulated interleukin 10 concentration, total antioxidant capacity, and mRNA expression of Nrf2 , Gsr , and Txn1 ( P < 0.01) in muscle. Exercise increased mRNA expression of Hmox1 compared with the control after 12 weeks ( P < 0.05). There were no significant differences between smoke groups for superoxide dismutase activity and Hmox1 mRNA expression. Exercise training improved the ability of skeletal muscle to adequately upregulate key antioxidant and anti-inflammatory defenses to detoxify electrophilic compounds induced by CS exposure, and these effects were more pronounced after 12 weeks. Novelty Exercise attenuates oxidative stress in skeletal muscle from animals exposed to CS via Nrf2 and glutathione pathways. Exercise is a helpful tool to control the inflammatory balance in skeletal muscle from animals exposed to CS. These beneficial effects were evident after 12 weeks.

Chronic exposure to ambient levels of air pollution induces respiratory illness exacerbation by increasing inflammatory responses and apoptotic cells in pulmonary tissues. The ineffective phagocytosis of these apoptotic cells (efferocytosis) by macrophages has been considered an important factor in these pathological mechanisms. Depending on microenvironmental stimuli, macrophages can assume different phenotypes with different functional actions. M1 macrophages are recognized by their proinflammatory activity, whereas M2 macrophages play pivotal roles in responding to microorganisms and in efferocytosis to avoid the progression of inflammatory conditions. To verify how exposure to air pollutants interferes with macrophage polarization in emphysema development, we evaluated the different macrophage phenotypes in a PPE- induced model with the exposure to diesel exhaust particles. C57BL/6 mice received intranasal instillation of porcine pancreatic elastase (PPE) to induce emphysema, and the control groups received saline. Both groups were exposed to diesel exhaust particles or filtered air for 60 days according to the groups. We observed that both the diesel and PPE groups had an increase in alveolar enlargement, collagen and elastic fibers in the parenchyma and the number of macrophages, lymphocytes and epithelial cells in BAL, and these responses were exacerbated in animals that received PPE instillation prior to exposure to diesel exhaust particles. The same response pattern was found inCaspase-3 positive cell analysis, attesting to an increase in cell apoptosis, which is in agreement with the increase in M2 phenotype markers, measured by RT-PCR and flow cytometry analysis. We did not verify differences among the groups for the M1 phenotype. In conclusion, our results showed that both chronic exposure to diesel exhaust particles and PPE instillation induced inflammatory conditions, cell apoptosis and emphysema development, as well as an increase in M2 phenotype macrophages, and the combination of these two factors exacerbated these responses. The predominance of the M2-like phenotype likely occurred due to the increased demand for efferocytosis. However, M2 macrophage activity was ineffective, resulting in emphysema development and worsening of symptoms., Competing Interests: The authors have declared that no competing interests exist.

Introduction: This study aimed to verify the effects of cigarette smoke exposure in bone mineralization and fibrillar matrix composition as well as in bone healing after tibial fracture induction., Methods: C57Bl/6 Mice were assigned according to exposure and surgery: C room air; F room air and tibia open osteotomy; CS cigarette smoke; FCS cigarette smoke and tibia open osteotomy. In order to study fracture healing we performed, under anesthesia, a bone injury through a tibial shaft osteotomy. Bone samples were obtained to evaluate bone histomorphometry, trabecular morphology and volume, trabecular collagen types composition and presence of inflammatory cytokines and growth factors., Results: CS exposure significantly reduced the thickness of bone trabeculae associated with decrease in mineralizing surface and mineral deposition rate, leading a lower bone formation rate and longer mineralization time. Resorption surface and osteoclastic surface were greater in the CS group, attesting increased resorptive action. There was a decrease in type I collagen deposition and genes expression in the CS and FCS groups compared to C group and in contrast there was an increase in type V collagen deposition and genes expression in the CS, FC and FSC groups compared to C group. Also, CS exposure induced a decrease in bone forming cytokines and an increase in inflammatory associated cytokines, and these changes were intensified under fracture conditions., Conclusion: Cigarette smoke exposure alters bone matrix composition and worsens bone mineralization, leading to bone fragility by increasing collagen V synthesis and deposition and impairing collagen I fibril forming and assembling. And these deleterious effects contributed to the worsening in fracture healing after tibia osteotomy., (Copyright © 2019. Published by Elsevier Inc.)

Chronic Obstructive Pulmonary Disease (COPD) is a syndrome that comprises several distinct and overlapping phenotypes. In addition to persistent airflow limitation and respiratory symptoms, COPD is also characterized by chronic systemic inflammation. Epidemiological studies have shown that dietary fibers, fruits and vegetables intake protects against the COPD development, while fructose-loading is associated with increased risk of asthma and chronic bronchitis. Since dietary factors might affect susceptibility to COPD by modulating oxidative stress and inflammatory responses, we evaluated how fructose feeding might affect the smoking-induced emphysema in mice. We found that chronic fructose intake induced destruction and remodeling of lung parenchyma and impairment of respiratory mechanics, which are associated with distinctive cytokine profiles in bronchoalveolar lavage fluid, blood plasma and skeletal muscle. The combined effects of chronic fructose intake and cigarette smoking on destruction of lung parenchyma are more pronounced than the effects of either alone. Excessive intake of fructose might directly cause pulmonary emphysema in mice rather than just altering its natural history by facilitating the installation of a low-grade systemic inflammatory milieu.

The benefits of moderate aerobic physical exercise for allergic asthma are well-known, particularly that of the anti-inflammatory effect that occurs by reducing Th2 responses and lung remodeling. However, the mechanisms of this immunoregulation are still under investigation. In this study, we investigated the possible immunoregulatory mechanisms of lung inflammation induced by moderate aerobic exercise in an experimental asthma model. BALB/c mice were distributed into Control, Exercise (EX), OVA, and OEX groups. OVA and OEX groups were sensitized with ovalbumin (OVA) on days 0, 14, 21, 28, and 42 and were challenged with OVA aerosol three times a week from days 21 to 51. The EX and OEX groups underwent moderate aerobic physical exercise from days 21 to 51 (5 d/w, 1 h/d). The mice were euthanized on day 52. We evaluated pulmonary cytokine production, serum immunoglobulin levels, and the inflammatory cell profile in lung and mediastinal lymph nodes. OVA mice showed increased expression of IL-4, IL-6, IL-10, and TGF-β and decreased macrophage type 2 (M2) recruitment. Physical exercise did not affect the increased antibody production of IgG2a, IgG1, or IgE induced by OVA. Of note, physical exercise alone markedly increased production of anti-inflammatory cytokines such as IL-10 and TGF-β. Physical exercise in OVA-mice also increased the recruitment of M2 in the lungs, as well as the influx and activation of regulatory T cells (Tregs) and CD4 and CD8 lymphocytes. In the draining lymph nodes, it was also observed that physical exercise increased the activation of CD4 T cells, regardless of the presence of OVA. Notably, physical exercise decreased common dendritic cells' (cDCs; pro-inflammatory) expression of co-stimulatory molecules such as CD80, CD86, and ICOSL in the draining lymph nodes, as well as increased ICOSL in plasmacytoid dendritic cells (pDCs; anti-inflammatory). Together, these findings show that physical exercise modulates pulmonary allergic inflammation by increasing Treg and M2 recruitment, as well as pDCs activation, which leads to an increase in anti-inflammatory cytokines and a decrease in pro-inflammatory cells and mediators.

We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 ± 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 µl) or lipopolysaccharide (LPS) (1 mg/kg in 50 µl of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4 + and CD8 + T cells, Treg cells, and IL-10 + and IL-17 + cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-γ, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4 + and CD8 + T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17 + cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5 + cells corroborated the increased numbers of IL-17 + and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL-10 + cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model.

A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk ( P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk ( P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs ( P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk ( P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation. NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators., (Copyright © 2017 the American Physiological Society.)

Objective:: To describe a murine model of emphysema induced by a combination of exposure to cigarette smoke (CS) and instillation of porcine pancreatic elastase (PPE)., Methods:: A total of 38 C57BL/6 mice were randomly divided into four groups: control (one intranasal instillation of 0.9% saline solution); PPE (two intranasal instillations of PPE); CS (CS exposure for 60 days); and CS + PPE (two intranasal instillations of PPE + CS exposure for 60 days). At the end of the experimental protocol, all animals were anesthetized and tracheostomized for calculation of respiratory mechanics parameters. Subsequently, all animals were euthanized and their lungs were removed for measurement of the mean linear intercept (Lm) and determination of the numbers of cells that were immunoreactive to macrophage (MAC)-2 antigen, matrix metalloproteinase (MMP)-12, and glycosylated 91-kDa glycoprotein (gp91phox) in the distal lung parenchyma and peribronchial region., Results:: Although there were no differences among the four groups regarding the respiratory mechanics parameters assessed, there was an increase in the Lm in the CS + PPE group. The numbers of MAC-2-positive cells in the peribronchial region and distal lung parenchyma were higher in the CS + PPE group than in the other groups, as were the numbers of cells that were positive for MMP-12 and gp91phox, although only in the distal lung parenchyma., Conclusions:: Our model of emphysema induced by a combination of PPE instillation and CS exposure results in a significant degree of parenchymal destruction in a shorter time frame than that employed in other models of CS-induced emphysema, reinforcing the importance of protease-antiprotease imbalance and oxidant-antioxidant imbalance in the pathogenesis of emphysema., Objetivo:: Descrever um modelo murino de enfisema induzido por exposição a fumaça de cigarro (FC) e instilação de elastase pancreática porcina (EPP)., Métodos:: Trinta e oito camundongos C57BL/6 foram aleatoriamente divididos em quatro grupos: controle (uma instilação intranasal de solução salina a 0,9%); EPP (duas instilações intranasais de EPP); FC (exposição a FC durante 60 dias) e FC + EPP (duas instilações intranasais de EPP + exposição a FC durante 60 dias). No fim do protocolo experimental, todos os animais foram anestesiados e traqueostomizados para o cálculo de parâmetros de mecânica respiratória. Em seguida, todos os animais foram sacrificados e seus pulmões foram removidos para a medição da intercepção linear média (Lm) e a determinação do número de células imunorreativas a antígeno macrofágico (MAC)-2, metaloproteinase da matriz (MMP)-12 e glicoproteína glicosilada de 91 kDa (gp91phox) no parênquima pulmonar distal e na região peribrônquica., Resultados:: Embora não tenha havido diferenças entre os quatro grupos quanto aos parâmetros de mecânica respiratória avaliados, houve aumento da Lm no grupo FC + EPP. O número de células positivas para MAC-2 na região peribrônquica e no parênquima pulmonar distal foi maior no grupo FC + EPP do que nos outros grupos, assim como o foi o número de células positivas para MMP-12 e gp91phox, porém somente no parênquima pulmonar distal., Conclusões:: Nosso modelo de enfisema induzido por instilação de EPP e exposição a FC resulta em um grau significativo de destruição parenquimatosa em um período de tempo menor que o empregado em outros modelos de enfisema induzido por FC, o que reforça a importância do desequilíbrio entre proteases e antiproteases e entre oxidantes e antioxidantes na patogênese do enfisema.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes ( p -cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae)., Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p -cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated., Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1β, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma ( p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide ( p < 0.05)., Conclusion: Monoterpenes p -cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.

The purpose of this study was to determine the effect of aerobic exercise training (AT) on the expression of glucocorticoid receptors (GR) and anti-inflammatory cytokines in an asthma model. BALB/c mice were divided into groups control (CT; nonsensitized/nontrained), aerobic training (AT; nonsensitized/trained), ovalbumin (OVA; sensitized/not trained), and OVA+AT (sensitized/trained). OVA groups received OVA by inhalation, and the AT groups completed 1, 3, or 7 days of exercise (60 min/session). Expression of GR, IL-4, IL-5, IL-10, IL-1ra, NF-κB, TGF-β, VEGF, ICAM-1, VCAM-1; eosinophils counting; and airway remodeling (AR) features [airway smooth muscle (ASM) and epithelial thickness and collagen fiber deposition] were quantified. OVA sensitization induced a decrease in the expression of GR and increases in the eosinophil, IL-4, IL-5, NF-κB, TGF-β, VEGF, ICAM-1, VCAM-1, and AR features (P < 0.05). After 3 days, AT reversed the OVA-induced reduction in the expression of GR, and subsequently induced increases in the expression of IL-10 and IL-1ra (seventh day). In contrast, the eosinophil migration, the expression of NF-κB, IL-4, IL-5, TGF-β, RANTES, VEGF, ICAM-1, VCAM-1, and the AR features (P < 0.05) were reduced. AT increases the expression of GR and anti-inflammatory cytokines (IL-10 and IL-1ra) and reduces the expression of inflammatory mediators and airway inflammation in an animal model of asthma., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD). However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI) to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group) or saline (SAL group) and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups). At day 28, the following analyses were performed: (I) lung mechanics, (II) exhaled nitric oxide (ENO), (III) bronchoalveolar lavage fluid (BALF), and (IV) lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

Background: Pulmonary emphysema is characterized by irreversible airflow obstruction, inflammation, oxidative stress imbalance and lung remodeling, resulting in reduced lung function and a lower quality of life. Flavonoids are plant compounds with potential anti-inflammatory and antioxidant effects that have been used in folk medicine. Our aim was to determine whether treatment with sakuranetin, a flavonoid extracted from the aerial parts of Baccharis retusa, interferes with the development of lung emphysema., Methods: Intranasal saline or elastase was administered to mice; the animals were then treated with sakuranetin or vehicle 2 h later and again on days 7, 14 and 28. We evaluated lung function and the inflammatory profile in bronchoalveolar lavage fluid (BALF). The lungs were removed to evaluate alveolar enlargement, extracellular matrix fibers and the expression of MMP-9, MMP-12, TIMP-1, 8-iso-PGF-2α and p65-NF-κB in the fixed tissues as well as to evaluate cytokine levels and p65-NF-κB protein expression., Results: In the elastase-treated animals, sakuranetin treatment reduced the alveolar enlargement, collagen and elastic fiber deposition and the number of MMP-9- and MMP-12-positive cells but increased TIMP-1 expression. In addition, sakuranetin treatment decreased the inflammation and the levels of TNF-α, IL-1β and M-CSF in the BALF as well as the levels of NF-κB and 8-iso-PGF-2α in the lungs of the elastase-treated animals. However, this treatment did not affect the changes in lung function., Conclusion: These data emphasize the importance of oxidative stress and metalloproteinase imbalance in the development of emphysema and suggest that sakuranetin is a potent candidate that should be further investigated as an emphysema treatment. This compound may be useful for counteracting lung remodeling and oxidative stress and thus attenuating the development of emphysema.

To describe the progression of parenchymal remodeling and metalloproteinases gene expression in earlier stages of emphysema, mice received porcine pancreatic elastase (PPE) instillation and Control groups received saline solution. After PPE instillation (1, 3, 6 hours, 3 and 21 days) we measured the mean linear intercept, the volume proportion of types I and III collagen, elastin, fibrillin and the MMP-1, -8, -12 and -13 gene expression. We observed an initial decrease in type I (at the 3rd day) and type III collagen (from the 6th hour until the 3rd day), in posterior time points in which we detected increased gene expression for MMP-8 and -13 in PPE groups. After 21 days, the type III collagen fibers increased and the type I collagen values returned to similar values compared to control groups. The MMP-12 gene expression was increased in earlier times (3 and 6 hours) to which we detected a reduced proportion of elastin (3 days) in PPE groups, reinforcing the already established importance of MMP-12 in the breakdown of ECM. Such findings will be useful to better elucidate the alterations in ECM components and the importance of not only metalloelastase but also collagenases in earlier emphysema stages, providing new clues to novel therapeutic targets.

The aim of this study was to investigate if the aerobic training (AT) reverses airway remodeling (AR) in an asthma model. BALB/c were divided into four groups: control (unsensitized and untrained); ovalbumin (OVA: sensitized and untrained); AT (unsensitized and trained) and OVA + AT. Allergic inflammation was induced with intraperitoneal and OVA inhalation. AT (low intensity; 5×/week; 60 min/session) was performed at 7, 15, and 30 days. Leukocyte counting in the bronchoalveolar lavage fluid; the expression of IL-5, eotaxin, RANTES, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1); AR features (airway smooth muscle, epithelium thickness, collagen and elastic fibers, mucus production); and AR inducers (transforming growing factor-beta, osteopontin, vascular endothelial growth factor). OVA induced an increase in leukocyte airway migration and increased AR features (P < 0.05). After 7 days, AT reversed the OVA-induced eosinophil and macrophage airway migration, the expression of IL-5, eotaxin, RANTES, ICAM-1, VCAM-1, and all AR inducers. However, total reversion of the AR features and inducers and airway inflammation occurred only after 15 days of AT compared with the OVA groups (P < 0.05) and the effects were maintained until the 30th day. AT reverses AR after 15 days and this effect is preceded by the inhibition of leukocyte migration and occurs simultaneously with the reduction in the expression of inflammatory mediators and AR inducers., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this study is to compare the effects of aerobic conditioning (AC) before (ACBS) and after (ACAS) allergic sensitization. BALB/c mice were divided into two main groups: ACBS and ACAS. Each groups was divided into subgroups: control (nonsensitized/nontrained), AC (nonsensitized/trained), ovalbumin (OVA) (sensitized/nontrained), AC+OVA (trained/sensitized), and OVA+AC (sensitized/trained). Sensitization was induced using OVA and AC performed in treadmill (moderate intensity). We examined IgE and IgG1 levels, eosinophil counting, expression of Th1 (interleukin (IL)-2, IFN-α) and Th2 cytokines (IL-4, IL-5, IL-13), IL-10, vascular endothelial growth factor (VEGF), and airway remodeling. IgE and IgG1 were decreased only when exercise was performed before sensitization (ACBS); however, there was a decrease of eosinophils, Th2 cytokines, VEGF, and airway remodeling and increase in IL-10 in either ACBS or ACAS groups. Our results demonstrate that aerobic conditioning reduces Th2 response before and after sensitization by increasing IL-10 while the production of anaphylactic antibodies is reduced only when exercise is performed before sensitization.

Aerobic exercise has been recognized as a stimulator of the immune system, but its effect on bacterial infection has not been extensively evaluated. We studied whether moderate aerobic exercise training prior to Streptococcus pneumoniae infection influences pulmonary inflammatory responses. BALB/c mice were divided into four groups: Sedentary Untreated (sedentary without infection); Sedentary Infected (sedentary with infection); Trained Untreated (aerobic training without infection); and Trained Infected (aerobic training with infection). Animals underwent aerobic training for 4 wk, and 72 h after last exercise training, animals received a challenge with S. pneumoniae and were evaluated either 12 h or 10 days after instillation. In acute phase, Sedentary Infected group had an increase in respiratory system resistance and elastance; number of neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BAL); polymorphonuclear cells in lung parenchyma; and levels of keratinocyte-derived chemokine (KC), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β (IL-1β) in lung homogenates. Exercise training significantly attenuated the increase in all of these parameters and induced an increase in expression of antioxidant enzymes (CuZnSOD and MnSOD) in lungs. Trained Infected mice had a significant decrease in the number of colony-forming units of pneumococci in the lungs compared with Sedentary Infected animals. Ten days after infection, Trained Infected group exhibited lower numbers of macrophages in BAL, polymorphonuclear cells in lung parenchyma and IL-6 in lung homogenates compared with Sedentary Infected group. Our results suggest a protective effect of moderate exercise training against respiratory infection with S. pneumoniae. This effect is most likely secondary to an effect of exercise on oxidant-antioxidant balance., (Copyright © 2014 the American Physiological Society.)

Aims: To determine whether a serine protease inhibitor treatment can prevent or minimize emphysema in mice., Methods: C57BL/6 mice were subjected to porcine pancreatic elastase (PPE) nasal instillation to induce emphysema and were treated with a serine protease inhibitor (rBmTI-A) before (Protocol 1) and after (Protocol 2) emphysema development. In both protocols, we evaluated lung function to evaluate the airway resistance (Raw), tissue damping (Gtis) and tissue elastance (Htis). The inflammatory profile was analyzed in the bronchoalveolar lavage (BALF) and through the use of morphometry; we measured the mean linear intercept (Lm) (to verify alveolar enlargement), the volume proportion of collagen and elastic fibers, and the numbers of macrophages and metalloprotease 12 (MMP-12) positive cells in the parenchyma. We showed that at both time points, even after the emphysema was established, the rBmTI-A treatment was sufficient to reverse the loss of elastic recoil measured by Htis, the alveolar enlargement and the increase in the total number of cells in the BALF, with a primary decrease in the number of macrophages. Although, the treatment did not control the increase in macrophages in the lung parenchyma, it was sufficient to decrease the number of positive cells for MMP-12 and reduce the volume of collagen fibers, which was increased in PPE groups. These findings attest to the importance of MMP-12 in PPE-induced emphysema and suggest that this metalloprotease could be an effective therapeutic target.

Maternal immunization with allergens, such as ovalbumin (OVA), can inhibit the development of an allergic response in offspring. The regulatory mechanisms seem to be mediated by maternal antibodies (MatAbs) and factors generated by the maternal-fetal interface. The aim of this study was to verify the pathways of inhibitory Ab transference after maternal immunization with OVA and the effect of the offspring's dendritic cells (DCs) on the generation of regulatory T (Treg) cells. We verified that preconceptional OVA immunization induces high levels of proinflammatory and regulatory cytokines in the amniotic fluid, allowing the transference of high levels of anti-OVA IgG1 Abs to the offspring. Using an adoptive nursing protocol, we verified that maternal immunization leads to MatAb transference by the placental route and by breastfeeding contribute to the inhibition of anaphylactic IgE and IgG1 Ab responses in immunized offspring. We observed that maternal immunization decreased eosinophil numbers in recovered bronchoalveolar lavage fluid and in the lung tissue, whereas with a lack of control of airway responsiveness to methacholine. Maternal immunization induced in young offspring a decreased percentage of CD11c+ DCs expressing MHC class II and CD40 molecules. Moreover, DCs from both groups of offspring when pulsed with OVA, were able to induce Treg cells in vitro. Similarly, OVA immunization at the neonatal stage increased the frequency of Treg cells, regardless of the mother's immunization status. These findings emphasize that maternal immunization leads to a complex interaction of regulatory factors, with MatAbs, DCs and Treg cells affecting the tolerance of offspring during an allergic response., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

A single instillation of porcine pancreatic elastase (PPE) results in significant airspace enlargement on the 28th day after instillation, whereas cigarette smoke (CS) exposure requires 6 months to produce mild emphysema in rodents. Considering that there are differences in the pathogenesis of parenchymal destruction in these different experimental models, it is likely that there may be different patterns of extracellular matrix (ECM) remodeling. To evaluate ECM remodeling, C57BL/6 mice were submitted to either a nasal drop of PPE (PPE 28 Days) or exposed for 6 months to cigarette smoke (CS 6 months). Control groups received either an intranasal instillation of saline solution (Saline 28 Days) or remained without any smoke inhalation for six months (Control 6 months). We measured the mean linear intercept and the volume proportion of collagen type I, collagen type III, elastin and fibrillin. We used emission-scanning confocal microscopy to verify the fiber distribution. Both models induced increased mean linear intercept in relation to the respective controls, being larger in the elastase model in relation to the CS model. In the CS model, emphysema was associated with an increase in the volume proportion of fibrillin, whereas in the PPE model there was an increase in the parenchymal elastin content. In both models, there was an increase in collagen type III, which was higher in the CS-exposed mice. We concluded that ECM remodeling is different in the two most used experimental models of emphysema.

We evaluated the effects of aerobic exercise (AE) on airway inflammation, exhaled nitric oxide levels (ENO), airway remodeling, and the expression of Th1, Th2 and regulatory cytokines in a guinea pig asthma model. Animals were divided into 4 groups: non-trained and non-sensitized (C), non-sensitized and AE (AE), ovalbumin-sensitized and non-trained (OVA), and OVA-sensitized and AE (OVA+AE). OVA inhalation was performed for 8 weeks, and AE was conducted for 6 weeks beginning in the 3rd week of OVA sensitization. Compared to the other groups, the OVA+AE group had a reduced density of eosinophils and lymphocytes, reduced expression of interleukin (IL)-4 and IL-13 and an increase in epithelium thickness (p<0.05). AE did not modify airway remodeling or ENO in the sensitized groups (p>0.05). Neither OVA nor AE resulted in differences in the expression of IL-2, IFN-γ, IL-10 or IL1-ra. Our results show that AE reduces the expression of Th2 cytokines and allergic airway inflammation and induces epithelium remodeling in sensitized guinea pigs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise improves the inflammatory status in different pulmonary diseases. However, the effects of long-term aerobic exercise on the pulmonary response to DEP have not been investigated. The present study evaluated the effect of aerobic conditioning on the pulmonary inflammatory and oxidative responses of mice exposed to DEP., Methods: BALB/c mice were subjected to aerobic exercise five times per week for 5 wk, concomitantly with exposure to DEP (3 mg·mL(-1); 10 μL per mouse). The levels of exhaled nitric oxide, reactive oxygen species, cellularity, interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were analyzed in bronchoalveolar lavage fluid, and the density of neutrophils and the volume proportion of collagen fibers were measured in the lung parenchyma. The cellular density of leukocytes expressing IL-1β, keratinocyte chemoattractant (KC), and TNF-α in lung parenchyma was evaluated with immunohistochemistry. The levels of IL-1β, KC, and TNF-α were also evaluated in the serum., Results: Aerobic exercise inhibited the DEP-induced increase in the levels of reactive oxygen species (P < 0.05); exhaled nitric oxide (P < 0.01); total (P < 0.01) and differential cells (P < 0.01); IL-6 and TNF-α levels in bronchoalveolar lavage fluid (P < 0.05); the level of neutrophils (P < 0.001); collagen density in the lung parenchyma (P < 0.05); the levels of IL-6, KC, and TNF-α in plasma (P < 0.05); and the expression of IL-1β, KC, and TNF-α by leukocytes in the lung parenchyma (P < 0.01)., Conclusions: We conclude that long-term aerobic exercise presents protective effects in a mouse model of DEP-induced lung inflammation. Our results indicate a need for human studies that evaluate the pulmonary responses to aerobic exercise chronically performed in polluted areas.

Objective: To verify the accordance of functional and morphometric parameters during the development of emphysema., Methods: BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days. Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed. To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma., Results: We only observed decreases in tissue elastance and tissue damping on the 28th day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema. However, only the mean linear intercept values remained increased until the 40th day. The volume proportion of collagen fibers was increased from the 15th day to the 40th day, whereas the volume proportion of elastic fibers was only increased on the 40th day. The number of macrophages increased beginning on the 1st day. The expression of metalloproteinase 12 was increased from the 3rd day until the 40th day. However, 8-isoprostane expression was only increased on the 1st and 3rd days., Conclusions: In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics. Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process.

Unlabelled: Our purpose in this study was to access the pulmonary effects of mechanical ventilation with positive end-expiratory pressure (PEEP; 10 cmH2O) or without PEEP (zero PEEP-ZEEP) in a rat model of acute myocardial infarction that resulted in hypotension but not in pulmonary congestion., Methods: Wistar rats were anesthetized (1.5% isoflurane) and myocardial infarct was induced by ligature of the anterior interventricular coronary artery. Rats with myocardial infarct were compared with sham-operated (Sham) and closed thorax groups., Results and Conclusion: There was a significant decrease in MAP in the acute myocardial infarct group (92.5 +/- 4.2 mmHg) when compared with closed chest group (113.0 +/- 4.4 mmHg). There was no significant difference between acute myocardial infarct and Sham groups in PEEP or ZEEP. Mechanical ventilation for 120 min resulted in a significant increase in respiratory system elastance in the groups ventilated with ZEEP (2.59 +/- 0.17 and 2.32 +/- 0.17 cmH2O.mL, Sham and acute myocardial infarct groups, respectively). This effect of mechanical ventilation was not observed in the presence of PEEP in both groups. There was no significant increase in the amount of perivascular pulmonary edema measured in all groups studied. Mean airspace linear intercept and lung tissue distortion index also did not show statistically significant difference between Sham and acute myocardial infarct groups. We conclude that in this experimental model of acute myocardial infarct (12.4 +/- 4.1% area of necrotic tissue and 26.4 +/- 4.0% area of ischemic tissue), there was a protective pulmonary effect of PEEP.