RESUMEN
Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA), an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1%) or vehicle (distillated water) during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure). Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.
Asunto(s)
Formaldehído/efectos adversos , Terapia por Luz de Baja Intensidad , Neumonía/etiología , Neumonía/radioterapia , Hipersensibilidad Respiratoria/complicaciones , Animales , Células de la Médula Ósea/metabolismo , Líquido del Lavado Bronquioalveolar , Degranulación de la Célula , Regulación de la Expresión Génica , Interleucina-6/genética , Interleucina-6/metabolismo , Pulmón/irrigación sanguínea , Pulmón/patología , Masculino , Mastocitos/metabolismo , Microvasos/patología , Neutrófilos/metabolismo , Permeabilidad , Neumonía/genética , Ratas Wistar , Hipersensibilidad Respiratoria/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Low-level laser therapy (LLLT) controls bronchial hyperresponsiveness (BHR) associated with increased RhoA expression as well as pro-inflammatory mediators associated with NF-kB in acute lung inflammation. Herein, we explore if LLLT can reduce both BHR and Th2 cytokines in allergic asthma. Mice were studied for bronchial reactivity and lung inflammation after antigen challenge. BHR was measured through dose-response curves to acetylcholine. Some animals were pretreated with a RhoA inhibitor before the antigen. LLLT (660 nm, 30 mW and 5.4 J) was applied on the skin over the right upper bronchus and two irradiation protocols were used. Reduction of BHR post LLLT coincided with lower RhoA expression in bronchial muscle as well as reduction in eosinophils and eotaxin. LLLT also diminished ICAM expression and Th2 cytokines as well as signal transducer and activator of transduction 6 (STAT6) levels in lungs from challenged mice. Our results demonstrated that LLLT reduced BHR via RhoA and lessened allergic lung inflammation via STAT6.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/efectos de la radiación , Asma/radioterapia , Broncoconstricción/efectos de la radiación , Citocinas/metabolismo , Hipersensibilidad/radioterapia , Terapia por Luz de Baja Intensidad , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Amidas/farmacología , Animales , Asma/tratamiento farmacológico , Asma/fisiopatología , Bronquios/efectos de los fármacos , Bronquios/fisiopatología , Bronquios/efectos de la radiación , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/fisiopatología , Hiperreactividad Bronquial/radioterapia , Broncoconstricción/efectos de los fármacos , Broncoconstricción/fisiología , Inhibidores Enzimáticos/farmacología , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/fisiopatología , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Pulmón/efectos de la radiación , Masculino , Ratones , Ratones Endogámicos BALB C , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiopatología , Músculo Liso/efectos de la radiación , Ovalbúmina/efectos adversos , Neumonía/tratamiento farmacológico , Neumonía/fisiopatología , Neumonía/radioterapia , Piridinas/farmacología , Factor de Transcripción STAT6/metabolismo , Proteínas de Unión al GTP rho/antagonistas & inhibidores , Proteínas de Unión al GTP rho/metabolismo , Proteína de Unión al GTP rhoARESUMEN
Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). It is not known if pro- and anti-inflammatory mediators in ARDS induced by i-I/R can be controlled by low-level laser therapy (LLLT). This study was designed to evaluate the effect of LLLT on tracheal cholinergic reactivity dysfunction and the release of inflammatory mediators from the lung after i-I/R. Anesthetized rats were subjected to superior mesenteric artery occlusion (45 min) and killed after clamp release and preestablished periods of intestinal reperfusion (30 min, 2 or 4 h). The LLLT (660 nm, 7.5 J/cm(2)) was carried out by irradiating the rats on the skin over the right upper bronchus for 15 and 30 min after initiating reperfusion and then euthanizing them 30 min, 2, or 4 h later. Lung edema was measured by the Evans blue extravasation technique, and pulmonary neutrophils were determined by myeloperoxidase (MPO) activity. Pulmonary tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1), and isoform of NO synthase (iNOS) mRNA expression were analyzed by real-time PCR. TNF-α, IL-10, and iNOS proteins in the lung were measured by the enzyme-linked immunoassay technique. LLLT (660 nm, 7.5 J/cm(2)) restored the tracheal hyperresponsiveness and hyporesponsiveness in all the periods after intestinal reperfusion. Although LLLT reduced edema and MPO activity, it did not do so in all the postreperfusion periods. It was also observed with the ICAM-1 expression. In addition to reducing both TNF-α and iNOS, LLLT increased IL-10 in the lungs of animals subjected to i-I/R. The results indicate that LLLT can control the lung's inflammatory response and the airway reactivity dysfunction by simultaneously reducing both TNF-α and iNOS.
Asunto(s)
Intestinos/irrigación sanguínea , Terapia por Luz de Baja Intensidad , Neumonía/radioterapia , Tráquea/fisiopatología , Tráquea/efectos de la radiación , Animales , Regulación de la Expresión Génica/efectos de la radiación , Mediadores de Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Peroxidasa/metabolismo , Neumonía/etiología , Neumonía/metabolismo , Edema Pulmonar/radioterapia , Ratas , Ratas Wistar , Reperfusión , Daño por Reperfusión/etiología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: It is unknown if pro- and anti-inflammatory mediators in acute lung inflammation induced by intestinal ischemia and reperfusion (i-I/R) can be modulated by low-level laser therapy (LLLT). STUDY DESIGN/MATERIAL AND METHODS: A controlled ex vivo study was developed in which rats were irradiated (660 nm, 30 mW, 0.08 cm² of spot size) on the skin over the right upper bronchus 1 hour post-mesenteric artery occlusion and euthanized 4 hours later. For pretreatment with anti-tumor necrosis factor (TNF) or IL-10 antibodies, the rats received either one of the agents 15 minutes before the beginning of reperfusion. METHODS: Lung edema was measured by the Evans blue extravasation and pulmonary neutrophils influx was determined by myeloperoxidase (MPO) activity. Both TNF and IL-10 expression and protein in lung were evaluated by RT-PCR and ELISA, respectively. RESULTS: LLLT reduced the edema (80.1 ± 41.8 µg g⻹ dry weight), neutrophils influx (0.83 ± 0.02 × 106 cells ml⻹), MPO activity (2.91 ± 0.60), and TNF (153.0 ± 21.0 pg mg⻹ tissue) in lung when compared with respective control groups. Surprisingly, the LLLT increased the IL-10 (0.65 ± 0.13) in lung from animals subjected to i-I/R. Moreover, LLLT (0.32 ± 0.07 pg ml⻹) reduced the TNF-α level in RPAECs when compared with i-I/R group. The presence of anti-TNF or IL-10 antibodies did not alter the LLLT effect on IL-10 (465.1 ± 21.0 pg mg⻹ tissue) or TNF (223.5 ± 21.0 pg mg⻹ tissue) in lung from animals submitted to i-I/R. CONCLUSION: The results indicate that the LLLT attenuates the i-I/R-induced acute lung inflammation which favor the IL-10 production and reduce TNF generation.
Asunto(s)
Interleucina-10/biosíntesis , Intestinos/irrigación sanguínea , Isquemia/complicaciones , Terapia por Luz de Baja Intensidad , Neumonía/radioterapia , Reperfusión , Factor de Necrosis Tumoral alfa/biosíntesis , Enfermedad Aguda , Animales , Edema , Láseres de Semiconductores/uso terapéutico , Pulmón/metabolismo , Pulmón/patología , Pulmón/efectos de la radiación , Masculino , Neutrófilos/efectos de la radiación , Peroxidasa/biosíntesis , Neumonía/etiología , Neumonía/metabolismo , Neumonía/patología , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Introdução: DPOC é uma enfermidade respiratória com manifestações sistêmicas que se caracteriza pela presença de obstrução crônica do fluxo aéreo, associada a uma resposta inflamatória. Objetivo: Verificar o efeito da laserterapia de laser 670nm, no tratamento da inflamação pulmonar induzida em ratos. Metodologia: 30 ratos foram divididos em três grupos, dos quais dois foram expostos à fumaça de cigarro durante 45 dias e um deles tratados com laser 670nm. Para análise dos resultados foram realizados LBA e ELISA. Resultados: Os resultados foram submetidos à análise de variância (ANOVA), seguida do teste Newman- Keuls para amostras não pareadas. A análise do LBA demonstrou um aumento altamente significativo no número de neutrófilos no grupo DPOC. O grupo tratado, quando comparado ao grupo DPOC, evidenciou uma diminuição significativa no número de neutrófilos. Para o resultado do ELISA, houve queda altamente significativa de TNF-?, quando tratado com laser 670nm, e significativa de MIP-2 e IL-1?. Conclusão: Verifica-se que a ação do laser de 670nm pode atenuar o processo inflamatório induzido.
Introduction: COPD is a respiratory illness with systemic manifestations, characterized by the presence of chronic airflow obstruction associated with an inflammatory response. Objective: To investigate the effect of laser 670nm laser in the treatment of pulmonary inflammation induced in mice. Methods: 30 rats were divided into three groups, two of which were exposed to cigarette smoke for 45 days and one treated with 670 nm laser. For data analysis and ELISA were performed BAL. Results: Results were subjected to analysis of variance (ANOVA) followed by Newman-Keuls test for unpaired samples. BAL analysis showed a highly significant increase in neutrophils in the COPD group. The treated group compared with the COPD group showed a significant decrease in neutrophils. For the result of the ELISA results were highly significant decrease of TNF-? when treated with 670 nm laser, and the significant MIP-2 and IL-1?. Conclusion: It appears that the action of the 670nm laser can attenuate the inflammatory process induced.
Asunto(s)
Animales , Masculino , Ratas , Enfermedad Pulmonar Obstructiva Crónica/radioterapia , Terapia por Luz de Baja Intensidad , Neumonía/radioterapia , Contaminación por Humo de Tabaco , Ratas Wistar , NeutrófilosRESUMEN
Introdução. A doença pulmonar obstrutiva crônica é uma enfermidade respiratória caracterizada pela presença de obstrução crônica do fluxo aéreo e manifestação inflamatória. Objetivo. Verificar o efeito da laserterapia de baixa potência no tratamento da inflamação pulmonar. Metodologia. Utilizou-se 30 ratos, divididos em três grupos de dez animais: grupo controle (recebeu apenas ar ambiente); grupo DPOC e grupo DPOC+laser (expostos à fumaça de cigarro durante 45 dias, sendo o grupo DPOC+laser tratado durante 12 dias com laser 904nm). Para análise dos resultados foi realizada histopatologia. Resultados. O grupo controle apresentou espaços aéreos normais com distorção arquitetural periférica do pulmão, o grupo DPOC demonstrou um enfisema acentuado, áreas de atelectasias e destruição das paredes alveolares. O grupo tratado houve uma regressão de enfisema acentuado para discreto. Conclusão. Na análise realizada, a inflamação pulmonar induzida pelo cigarro pode ser comprovada e a laserterapia de baixa potência mostrou-se eficaz na atenuação da inflamação.
Introduction. The chronic obstructive pulmonary disease is a respiratory disease characterized by chronic airflow obstruction and inflammatory manifestation. Objective. To investigate the effect of low level laser therapy in the treatment of pulmonary inflammation. Methodology. We used 30 rats divided into three groups of ten animals: control group (received only room air), group COPD and COPD + laser (exposed to cigarette smoke for 45 days with group COPD + laser treated for 12 days with 904nm laser). For data analysis was performed histopathology. Results. The control group had normal air spaces with architectural distortion of the peripheral lung, COPD group showed a marked emphysema, areas of atelectasis and destruction of alveolar walls in the treated group there was a regression from mild to severe emphysema. Conclusion. Through the analysis performed pulmonary inflammation induced by cigarette can be proved, and the low level laser therapy was effective in reducing inflammation.
Asunto(s)
Animales , Masculino , Ratas , Neumonía/radioterapia , Terapia por Luz de Baja Intensidad , Atelectasia Pulmonar , Contaminación por Humo de Tabaco , Epidemiología Descriptiva , Ratas Wistar , Enfisema/radioterapiaRESUMEN
It has been suggested that low intensity laser therapy (LILT) acts on pulmonary inflammation. Thus, we investigate in this work if LILT (650nm, 2.5mW, 31.2mW/cm(2), 1.3J/cm(2), laser spot size of 0.08cm(2) and irradiation time of 42s) can attenuate edema, neutrophil recruitment and inflammatory mediators in acute lung inflammation. Thirty-five male Wistar rats (n=7 per group) were distributed in the following experimental groups: control, laser, LPS, LPS+laser and dexamethasone+LPS. Airway inflammation was measured 4h post-LPS challenge. Pulmonary microvascular leakage was used for measuring pulmonary edema. Bronchoalveolar lavage fluid (BALF) cellularity and myeloperoxidase (MPO) were used for measuring neutrophil recruitment and activation. RT-PCR was performed in lung tissue to assess mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin (IL-10), cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage inflammatory protein-2 (MIP-2) and intercellular adhesion molecule-1 (ICAM-1). Protein levels in both BALF and lung were determined by ELISA. LILT inhibited pulmonary edema and endothelial cytoskeleton damage, as well as neutrophil influx and activation. Similarly, the LILT reduced the TNF-α and IL-1ß, in lung and BALF. LILT prevented lung ICAM-1 up-regulation. The rise of CINC-1 and MIP-2 protein levels in both lung and BALF, and the lung mRNA expressions for IL-10, were unaffected. Data suggest that the LILT effect is due to the inhibition of ICAM-1 via the inhibition of TNF-α and IL-1ß.
Asunto(s)
Quimiocinas/metabolismo , Citocinas/metabolismo , Terapia por Luz de Baja Intensidad , Neutrófilos/efectos de la radiación , Neumonía/radioterapia , Enfermedad Aguda , Aerosoles/química , Animales , Antiinflamatorios/farmacología , Líquido del Lavado Bronquioalveolar , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Quimiocinas/genética , Citocinas/genética , Dexametasona/farmacología , Modelos Animales de Enfermedad , Escherichia coli/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolisacáridos/toxicidad , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Masculino , Neutrófilos/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Low level laser therapy (LLLT) is a known anti-inflammatory therapy. Herein we studied the effect of LLLT on lung permeability and the IL-1beta level in LPS-induced pulmonary inflammation. STUDY DESIGN/METHODOLOGY: Rats were divided into 12 groups (n = 7 for each group). Lung permeability was measured by quantifying extravasated albumin concentration in lung homogenate, inflammatory cells influx was determined by myeloperoxidase activity, IL-1beta in BAL was determined by ELISA and IL-1beta mRNA expression in trachea was evaluated by RT-PCR. The rats were irradiated on the skin over the upper bronchus at the site of tracheotomy after LPS. RESULTS: LLLT attenuated lung permeability. In addition, there was reduced neutrophil influx, myeloperoxidase activity and both IL-1beta in BAL and IL-1beta mRNA expression in trachea obtained from animals subjected to LPS-induced inflammation. CONCLUSION: LLLT reduced the lung permeability by a mechanism in which the IL-1beta seems to have an important role.
Asunto(s)
Permeabilidad Capilar/efectos de la radiación , Interleucina-1beta/metabolismo , Terapia por Luz de Baja Intensidad , Pulmón/efectos de la radiación , Infiltración Neutrófila/efectos de la radiación , Neutrófilos/efectos de la radiación , Neumonía/radioterapia , Tráquea/efectos de la radiación , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Permeabilidad Capilar/efectos de los fármacos , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Interleucina-1beta/genética , Lipopolisacáridos , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Pulmón/inmunología , Masculino , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Peroxidasa/metabolismo , Neumonía/inducido químicamente , Neumonía/inmunología , Neumonía/metabolismo , Reacción en Cadena de la Polimerasa , Proteínas/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores de Interleucina/antagonistas & inhibidores , Receptores de Interleucina/metabolismo , Factores de Tiempo , Tráquea/efectos de los fármacos , Tráquea/inmunología , TraqueotomíaRESUMEN
O transplante de medula óssea (TMO) tem sido utilizado como tratamento de escolha para diversas doenças hematológicas. Entretanto, as complicações pulmonares, que podem ocorrer em até 60 por cento dos pacientes, são o principal motivo de falha no tratamento. As complicações pulmonares pós-TMO podem ser divididas em três fases, de acordo com a imunidade do paciente. Na primeira fase, até 30 dias após o procedimento, predominam as complicações não infecciosas e as pneumonias fúngicas. Na fase precoce, que vai até o 100º dia pós-TMO, as infecções virais, principalmente por citomegalovírus, são mais comuns. Finalmente, na fase tardia pós-TMO, complicações não infecciosas como bronquiolite obliterante com pneumonia em organização e doença do enxerto contra o hospedeiro são mais comumente observadas. Os autores apresentam um ensaio iconográfico, enfatizando os aspectos de tomografia de alta resolução em pacientes com complicações pulmonares pós-TMO.
Bone marrow transplantation has been the treatment of choice for many hematologic diseases. However, pulmonary complications, which may occur in up to 60% of the patients, are the main cause of treatment failure and may be divided in three phases according to the patient's immunity. In the first phase, up to 30 days after the procedure, there is a predominance of non-infectious complications and fungal pneumonia. Viral infections, mainly by cytomegalovirus, are common in the second phase (up to 100 days after bone marrow transplantation). Finally, in the late phase after bone marrow transplantation, non-infectious complications as bronchiolitis obliterans organizing pneumonia and graft-versus-host disease are most commonly seen. The authors present a pictorial essay of the high-resolution computed tomography findings in patients with pulmonary complications after bone marrow transplantation.
Asunto(s)
Humanos , Trasplante de Médula Ósea , Enfermedades Hematológicas/cirugía , Neumonía/radioterapia , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/radioterapia , Trasplante de Médula Ósea/efectos adversos , Diagnóstico por Imagen , Tomografía Computarizada por Rayos XRESUMEN
The purpose of this study was to investigate the effect of low level laser therapy (LLLT) on male Wistar rat trachea hyperreactivity (RTHR), bronchoalveolar lavage (BAL) and lung neutrophils influx after Gram-negative bacterial lipopolyssacharide (LPS) intravenous injection. The RTHR, BAL and lung neutrophils influx were measured over different intervals of time (90 min, 6 h, 24 h and 48 h). The energy density (ED) that produced an anti-inflammatory effect was 2.5 J/cm(2), reducing the maximal contractile response and the sensibility of trachea rings to methacholine after LPS. The same ED produced an anti-inflammatory effect on BAL and lung neutrophils influx. The Celecoxib COX-2 inhibitor reduced RTHR and the number of cells in BAL and lung neutrophils influx of rats treated with LPS. Celecoxib and LLLT reduced the PGE(2) and TXA(2) levels in the BAL of LPS-treated rats. Our results demonstrate that LLLT produced anti-inflammatory effects on RTHR, BAL and lung neutrophils influx in association with inhibition of COX-2-derived metabolites.