Introduction: Rheumatoid arthritis (RA) is a multisystem disease associated with early mortality. Methotrexate (MTX) is the first-line therapy in RA but is associated with significant adverse events and response is not universal. There is, therefore, a need to identify early those patients with RA unlikely to respond or develop toxicity to MTX. One of the major influences on drug response is adherence and MTX can cause a range of side effects known to impact on adherence such as pneumonitis (MTX-P). The gold standard measurement of adherence would be direct detection of MTX or its metabolites in a biochemical assay. Currently, there are no reliable markers that predict response to MTX but some studies have suggested measurement of MTX levels may predict response. Previous studies have suggested that MTX-P may occur in individuals genetically predisposed to the disease. The aims of this research are to i) develop an assay to measure MTX levels; ii) test the ability of the assay to measure adherence; iii) investigate if MTX levels are associated with response; and iv) conduct a genome wide association study (GWAS) investigating MTX-P. Methods: An assay to measure MTX and 7-OH-MTX in urine and plasma was developed using HPLC-SRM-MS and the assay was used to measure levels in a cohort of RA patients to develop a pharmacokinetic model. Simulations of the model were used to determine the ability of the assay to monitor adherence and the model was validated in a separate cohort of patients with RA. An observational study of RA patients was used to measure MTX and 7-OH-MTX levels to investigate if levels are associated with response. Finally, a GWAS investigating MTX-P was conducted. Results: Results of the pharmacokinetic model demonstrated that MTX is the preferred analyte to monitor adherence. The model was validated in a separate cohort of patients with RA demonstrating the ability of the assay to measure adherence. MTX levels were not associated with disease response in this cohort. A GWAS of MTX-P demonstrated three SNPs associated with disease (p <5 x 10-5) with subsequent bioinformatics analysis showing a potential functional role for rs7514182.ConclusionAdherence to MTX may be a significant barrier to patients achieving full response to therapy. The development of a direct test to detect adherence based on measuring MTX levels using HPLC-SRM-MS has been developed in urine and blood. The assay was shown to be accurate in several domains from EMA guidelines and was validated in a separate cohort of patients. Finally, this program of work has investigated genetic markers associated with MTX-P. The results demonstrated a potential SNP associated with disease which demonstrates a functional role in the development of pulmonary fibrosis.

Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.

Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.

Orientador: Maria Rita de Camargo Donalisio Cordeiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T12:22:51Z (GMT). No. of bitstreams: 1 Arca_CarlosHenriqueMamud_M.pdf: 1498465 bytes, checksum: 064c200d1dd6b96e35ec6db322d7e8c6 (MD5) Previous issue date: 2008 / Resumo: Pneumonia Adquirida na Comunidade (PAC) é aquela que acomete o paciente fora do ambiente hospitalar ou que surge nas primeiras 48 horas da internação. A pneumonia é uma doença grave associada a significativa morbidade e mortalidade em adultos e sua taxa de mortalidade hospitalar vem crescendo, apesar dos avanços dos meios diagnósticos e terapêuticos. Neste contexto, o estabelecimento das características clínicas e microbiológicas da PAC, numa determinada região, pode trazer melhorias no seu manejo com impacto econômico e social. O objetivo deste estudo foi analisar os fatores de risco relacionados com o óbito e a evolução clínica da PAC, considerando-se o seu perfil microbiológico, sua relação com antecedentes epidemiológicos, vacinais e variáveis clínicas. Foi realizado um estudo descritivo prospectivo dos casos de PAC (61) em indivíduos maiores de 14 anos admitidos no Hospital Estadual Sumaré (HES), referência para atendimento hospitalar da microrregião de Sumaré, SP, no período de outubro de 2005 a setembro de 2007. Foi ajustado modelo de regressão logística múltipla, tendo-se como variável dependente evolução desfavorável, isto é, aqueles com internação maior que 10 dias, necessidade de internação em UTI ou óbitos. Não houve associação entre sexo, tabagismo, etilismo, passado vacinal ou presença de comorbidades com a evolução desfavorável do caso. Mudança de antibioticoterapia (RR = 2,22; IC 95%: 1,32 - 3,72), necessidade de fisioterapia respiratória (RR = 2,42; IC 95%: 1,21 - 4,87) e utilização de oxigenioterapia (RR = 2,40; IC 95%: 1,45 - 3,99) apresentaram associação com caso grave. Valores alterados de creatinina (p=0,05) e albumina (p=0,01) séricas foram identificados como fatores de risco relacionados com evolução desfavorável. A etiologia foi definida em 57,4% dos casos. O Streptococcus pneumoniae (19,7%) foi o agente de maior expressividade seguido da Chlamydophila pneumoniae (16,4%). Receberam alta hospitalar por cura, 80,3% dos pacientes e foram registrados três óbitos (4,9%). Embora a casuística deste estudo seja limitada, os achados demonstraram que o perfil microbiológico local reflete os apontados na literatura, e permitiram identificar a creatinina sérica e a albumina sérica como fatores de risco, possivelmente relacionados com evolução desfavorável da PAC na população estudada / Abstract: Community Acquired Pneumonia (CAP) is the one which is contracted by the patient outside hospital environment or manifests itself in the first 48 hours after first being admitted in the facility. Pneumonia is a severe disease associated with high mortality and morbidity ratings in adults and these ratings have been increasing despite advancements in diagnostic and therapeutic techniques. In this context, establishing the clinic and microbiologic characteristics of CAP, in a certain region, may result in advancements in the handling of its economical and social impact. The objective of this study was to analyze the risk factors related to death in CAP¿s clinical evolution, to study its microbiologic factors, its epidemiologic and vaccination background and clinical variables, besides the cases evolution. A descriptive prospective study of CAP¿s cases (61) was conducted in individuals with more than 14 years of age, admitted in the Hospital Estadual de Sumaré (HES), a reference in hospital treatment in Sumaré¿s micro region, SP, from October 2005 to September 2007. A multiple logistic regression model was adjusted, having as dependent variable unfavorable evolution (cases in which the hospitalization period was greater than 10 days or resulted in death). There was no association between gender, smoking, drinking, vaccination background or presence of comorbities in the unfavorable outcome of the cases. Changes in the antibiotic therapy (RR = 2.22; IC 95%: 1.32 ¿ 3.72), necessity of respiratory physiotherapy (RR = 2.42; IC 95%: 1.21 ¿ 4.87) and oxygen therapy (RR = 2.40; IC 95%: 1.45 ¿ 3.99) presented association with severe cases. The etiology was defined in 57.4% of the cases. Streptococcus pneumoniae (19.7%) was the agent with the highest expressiveness, followed by Chlamydophila pneumoniae (16.4%). The percentage of patients discharged after being cured was 80.3 % and three deaths were registered (4.9%). Although this study¿s casuistry was limited, the findings demonstrated that the local microbiologic profile reflects those in medical literature, and allowed the identification of blood creatinine (p=0.05) and albumin (p=0.01) as risk factors related to unfavorable evolution in CAP concerning the studied population / Mestrado / Epidemiologia / Mestre em Saude Coletiva

Dabbing has been gaining popularity among young people in recent years due to its ability to deliver a high concentration of tetrahydrocannabinol. When produced illegally, it is usually contaminated by toxic substances and associated with multiple health hazards. We present the case of a 66-year-old woman who developed hypersensitivity pneumonitis after dabbing butane hash oil for the first time and was successfully treated with corticosteroids with complete resolution of her symptoms. This case report emphasizes the respiratory complications associated with using a noxious substance like butane hash oil and gives physicians an insight into the diagnosis and management of dabbing-induced hypersensitivity pneumonitis.

Bronchoalveolar lavage (BAL) is an established method providing diagnostic support and evaluation of disease activity in interstitial lung disease (ILD). The aims of the present investigation were 1) to study the inflammatory response in pneumonitis evoked by irradiation. 2) to evaluate how well lung tissue inflammation is reflected in BAL findings. 3) to study the effect of smoking on radiation-induced pneumonitis. BAL was performed in 21 patients (11 smokers, 10 non-smokers) who were treated for breast cancer, stage 1 (TjMaNq) by post-surgery irradiation to an accumulated target dose of 56 Gy. It was founa that irradiation induced an alveolitis in the non-smoking patient group while the smoking patients did not differ from their smoking controls. The alveolitis in non-smokers was characterized by an increase in lymphocytes, mast cells and elevated concentrations of hyaluronan (HA), and fibronectin (FN). Three of the non-smoking patients had chest X-ray infiltrates indicating the presence of pneumonitis. An animal experimental model for radiation-induced pneumonitis and fibrosis was established in rats, allowing comparative analysis of BAL fluid and morphology. In the rat model a divergence was noted between the differential cell counts in BAL and cells observed in the interstitial tissue, which was most notable for neutrophils (PMN) and mast cells whereas there was a good correlation between HA content in BAL and HA deposition in the lung tissue. A marked infiltration of intraseptally-located mast cells occurred during the pneumonitis-phase, and this increase was paralleled by a deposition of HA in the interstitial tissue. Histochemical fixation and staining properties of the mast cells revealed that the majority of these cells were of connective tissue mast cell type (CTMC). Compound 48/80, a mast cell secretagogue, significantly altered the HA content both in BAL and in lung tissue in the irradiated animals. Regular treatment throughout the whole experimental period induced depletion of mast cell granules and a decrease in HA deposition whereas 48/80 treatment during the pneumonitis phase enhanced HA deposition. A rat model with smoke exposure was developed, and the effect of cigarette smoke on radiation-induced inflammation was studied. Rats that smoked 3 weeks prior to irradiation and continued to smoke throughout the observation period (7 weeks) had a significantly reduced inflammatory response compared to irradiated non-smoking rats. The most prominent BAL findings in the smoke-exposed rats were a decrease in PMN, mast cells and a decrease in HA. In conclusion, irradiation induces an alveolitis characterized mainly by mononuclear cells. Mast cells seem to be of importance in the remodelling of the connective tissue in the radiation-induced inflammatory response. Hyaluronan is an important component in the early connective tissue response preceding later collagen deposition, and its interstitial deposition is very well reflected in BAL. Moreover, tobacco-smoke suppresses the radiation-induced inflammation with a decreased recruitment of effector cells including mast cells. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1992, härtill 5 uppsatser.</p> / digitalisering@umu

Σκοπός της παρούσας μελέτης ήταν να εκτιμηθούν οι πιθανές οξείες μεταβολές των πνευμονικών λειτουργιών σε γυναίκες που υποβλήθηκαν σε μετεγχειρητική ακτινοθεραπεία για καρκίνο του μαστού μετά από συντηρητική επέμβαση διατήρησης του μαστού ή μετά από μαστεκτομή. Η μελέτη συμπεριλάμβανε 35 γυναίκες εκ των οποίων οι 21 από αυτές είχαν υποβληθεί και σε χημειοθεραπεία. Από το συνολικό δείγμα των 35 γυναικών, οι 14 υποβλήθηκαν και σε ακτινοθεραπεία της μασχαλιαίας και της υπερκλείδιας χώρας λόγω διηθημένων μασχαλιαίων λεμφαδένων. Όλες οι γυναίκες που έλαβαν μέρος στη μελέτη υποβλήθηκαν σε έλεγχο της πνευμονικής λειτουργίας με τη μέτρηση της βίαιης ζωτικής χωρητικότητας (FVC), του βίαιου εκπνεόμενου όγκου αέρα σε 1 sec (FEV1), της μέγιστης μεσοεκπνευστικής ροής (MMEF25-75), της μέγιστης κατανάλωσης οξυγόνου (VO2max), και της διαχυτικής ικανότητας μονοξειδίου του άνθρακα (DLCO). Όλες οι παραπάνω παράμετροι μετρήθηκαν πριν από την έναρξη της ακτινοθεραπείας και τρείς μήνες μετά από την ολοκλήρωσή της. Από την στατιστική ανάλυση προέκυψε στατιστικά σημαντική πτώση των τιμών των FVC, FEV1 και του DLCO, τρείς μήνες μετά την ολοκλήρωση της ακτινοθεραπείας, στις γυναίκες που έλαβαν τοπικοπεριοχική ακτινοθεραπεία και χημειοθεραπεία. Ωστόσο, στις γυναίκες που έλαβαν αποκλειστικά τοπική ακτινοθεραπεία δεν παρατηρήθηκε στατιστικά σημαντική πτώση των παραπάνω τιμών. Συμπερασματικά, η τοπική ακτινοθεραπεία για τον καρκίνο του μαστού δεν συσχετίστηκε με στατιστικά σημαντική πτώση των τιμών των πνευμονικών λειτουργιών, ενώ η τοπικοπεριοχική ακτινοβόληση και η χορήγηση χημειοθεραπείας ανέδειξε στατιστικά σημαντική πτώση των FVC, FEV1 και του DLCO τρείς μήνες μετά την ολοκλήρωση της ακτινοθεραπείας. / The frequency and grade of pulmonary complications after radiotherapy for breast cancer are still debated. This study evaluated changes in pulmonary function tests (PFTs) after radiotherapy in women with breast cancer. Thirty five consecutive eligible women with breast cancer underwent pulmonary function testing before and 3 months after adjuvant radiotherapy. Twenty one of them also received chemotherapy. A significant decrease of forced vital capacity, forced expiratory volume in one second and carbon monoxide diffusing capacity was observed in the women treated with locoregional adjuvant radiotherapy and chemotherapy, whereas no decrease of the above parameters was evidenced in women treated exclusively with local adjuvant radiotherapy. Local adjuvant radiotherapy is not associated with any reduction in lung function parameters, however, locoregional adjuvant radiotherapy combined with chemotherapy shows a significant reduction in PFTs 3 months after radiotherapy completion.

Les pneumopathies d'hypersensibilité sont des maladies respiratoires liées à l'inhalation répétée de substances antigéniques. Le diagnostic nécessite la présence d'un ensemble d'arguments cliniques, radiologiques, fonctionnels et immunologiques car les symptômes sont peu spécifiques. La mise en évidence d'immunoglobulines G (IgG) spécifiques des agents étiologiques est un élément essentiel dans la prise en charge diagnostique et thérapeutique. L'objectif de ce travail de thèse était d'identifier des protéines bactériennes et fongiques reconnues par les IgG des patients atteints de la maladie du poumon de fermier (PDF) et du poumon de mécanicien (FDM), et de produire ces protéines de façon recombinante afin de développer des tests sérologiques standardisés de type ELISA. Deux micro-organismes impliqués dans le PDF (Saccharopolyspora rectivirgula et Eurotium amstelodami, un Aspergillus), et un micro-organisme impliqué dans le PDM (Mycobacterium immunogenum) ont été étudiés. L'approche immunoprotéomique développée a permis de sélectionner les protéines d'intérêt, puis de produire les antigènes recombinants correspondants par génie génétique. Des sérums de patients PDF, PDM et de témoins exposés ont été recueillis dans le cadre de protocoles cliniques multicentriques. Les performances (sensibilité, spécificité, aire sous la courbe) des tests ELISA-IgG utilisant les antigènes recombinants produits ont été évaluées par l'analyse en courbe ROV (Receiver operating characteristics). A partir des trois micro-organismes étudiés, 71 protéines immuno-réactives ont été identifiées et 28 protéines recombinantes ont été produites et testées en ELISA. Pour le diagnostic du PDM, deux antigènes recombinants, la dihydrolipoyl déshydrogénase and Facyl-CoA déshydrogénase, étaient particulièrement performants avec une sensibilité de 90% lorsqu'ils étaient utilisés en combinaison. Pour le diagnostic du PDF, deux antigènes recombinants à'Aspergillus, la Glu/Leu/Phe/Val déshydrogénase et la glucose-6-phosphate isomérase, ont permis d'obtenir une sensibilité de 89% et une spécificité de 84%. L'utilisation de trois antigènes recombinants de S. rectivirgula,SRl¥A (protéine de fonction inconnue), SRI? (catalase) et SR22 (kétol acide réducto-isomérase), ont permis d'obtenir une sensibilité et spécificité optimales de 83% et 77%. Les protéines identifiées étaient majoritairement des protéines enzymatiques, dont certaines ont été mis en évidence comme facteurs de virulence dans d'autres pathologies. Des études complémentaires, sur des modèles animaux et sur des modèles cellulaires, devront être mennées pour explorer l'implication de ces protéines dans l'induction de la maladie. Ce travail a permis d'améliorer les connaissances sur les protéines bactériennes et fongiques reconnues par les anticorps des patients atteints de PDF et de PDM, de développer des antigènes recombinants, et de mettre au point des tests sérologiques standardisés et performants. Ces tests pourront faire l'objet d'une valorisation vers l'industrie. En effet, les sérologies pour le diagnostic des PHS sont des demandes courantes dans les laboratoires d'analyse médicale. / The hypersensitivity pneumonitis is a pulmonary disease caused by repetitive inhalation of antigens. The diagnosis requires clinical, radiological, functional and immunological features because of unspecific symptoms. The identification of specifie antibodies to causative antigens is an essential way for the diagnosis and therapeutic management.The aims of this thesis work were to identify bacterial and fungal immunogenic proteins specifie to patient with farmer's lung (FL) and machine operator's lung (MOL) diseases, to synthesize specifie recombinant antigens for the development of a standardized ELISA. Two microorganisms involved in FL (Saccharopolyspora rectivirgula and Eurotium amstelodami (Aspergillus sp)), and one involved in MOL had been srudied. The immunoproteomics approach has permit to select interesting proteins and to synthesize recombinant antigens by genomics techniques. The sera from FL patients (n=52), MOL patients (n=16) and sera from exposed control subjects were recruited. ELISA-IgG using recombinant antigens efficacies were evaluated by Receiver operating characteristics analysis (sensitivity, specifïcity, area under the curve).From the three srudied microorganisms, 71 immunogenic proteins were identified and 28 recombinant antigens were produced and tested by ELISA. For the MOL diagnosis, the recombinants dihydrolipoyl dehydrogenase and acyl-CoA dehydrogenase were useful with a sensitivity of 90% when used in combination. For the FL diagnosis, two recombinant proteins from Aspergillus, Glu/Leu/Phe/Val dehydrogenase and glucose-6-phosphate isomerase had a sensitivity of 89% and a specifïcity of 84%. A combination of the three recombinant antigens from S. rectivirgula, SRI FA (unknown function), SRI 7 (catalase) and SR22 (ketol acid reductoisomerase) allowed to obtain a sensitivity of 83% and a specificity of 77%. The immunogenic proteins were mainly enzymes, and some of these have been implicated in important functions for survival or the virulence of others pathogens. Further studies are required to determine the role of these proteins in immunological or virulence processes by animal and cellular model application. This present work has improved our knowledge about bacterial and fungal proteins recognized by FL and MOL patient's antibodies, and to develop useful standardized serological tests with new recombinant antigens. These tests could be exported to the health management in industry. Indeed, hypersensitivity pneumonitis serodiagnosis tests are common requests in medical analysis laboratories

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20997号 / 医博第4343号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 鈴木 実, 教授 平井 豊博, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Orientador: Luiz Roberto Lopes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T19:36:32Z (GMT). No. of bitstreams: 1 Bianchi_RenataCristianeGennari_D.pdf: 1264896 bytes, checksum: e7f0d2b827693233f95ddfd5a5e1ab93 (MD5) Previous issue date: 2012 / Resumo: As neoplasias esofágicas passíveis de tratamento por radioterapia podem induzir seqüelas clínicas importantes como a pneumonite radioinduzida e a fibrose pulmonar. É sabido que os exercícios físicos promovem uma seqüência de liberação de citocinas pró-inflamatórias, com diminuição dos efeitos deletérios das desordens cardiovasculares e promoção de efeito protetor contra as doenças associadas à inflamação sistêmica. Diante deste fato, o presente estudo teve o objetivo de verificar se a atividade física pré-radioterapia possui elementos radioprotetores, medindo-se a ativação de citocinas pró-inflamatórias como a interleucina-6 (IL-6), fator transformador de crescimento-bete (TGF-'beta'), fator de necrose tumoral-alfa (TNF-'alfa') e quinase de proteína beta (IKK'beta'), por meio da análise de Western Blotting (WB). Para isto, foi realizado um estudo randomizado empregando 28 ratos Wistar Hannover, machos, com idade média de 90 dias e e peso aproximado de 200 gramas. Os animais foram divididos em 3 grupos. Gl (grupo controle), Gll (grupo que foi submetido à radioterapia e sacrificado no 1o dia pós-radioterapia - Glla ou sacrificado no 7o dia pós-radioterapia - Gllb) e Glll (grupo que realizou atividade física e radioterapia e foi sacrificado no 1°dia pós-radioterapia- Gllla ou sacrificado no 7°dia pós-radioterapia- Glllb). A atividade física do grupo Glll consistiu em natação, durante 8 semanas (carga zero, 3 vezes por semana, cerca de 30 minutos). Após tal atividade física, Gll e Glll foram submetidos à irradiação por cobaltoterapia, dose única de 3,5 grays em corpo inteiro. Todos os animais foram sacrificados por overdose de pentobarbital, de acordo com o tempo de análise de citocinas, e em seguida, um fragmento do lobo inferior do pulmão direito foi foi analisado por WB. Como resultado, a expressão das citocinas IKK'beta', TNF-'alfa' e IL-6 induzidas por radiação no pulmão foi menor nos animais que se exercitaram e que foram sacrificados no 7°dia pós-radioterapia (Glllb), com significância estatística através do teste de ANOVA (p<0,05). No entanto, o exercício não alterou o aumento induzido pela radiação em relação à TGF-'beta'. Concluiu-se que a atividade física possui elementos radioprotetores, pois houve menor aumento de IKK'beta', TNF-'alfa' e IL-6 nos grupos pós-atividade física (Glllb), com sugestão de menor inflamação e lesão tecidual pós-radioterapia. Possivelmente não houve significância estatística em relação à TGF-'beta', pois tal citocina tem papel preponderante numa fase mais tardia de injúria tecidual, ou seja, na fibrose pulmonar. Além disso, as citocinas analisadas mostraram-se bons marcadores para mensurar a resposta inflamatória tecidual pulmonar / Abstract: Esophageal neoplasms amenable to treatment by radiation therapy may induce important clinical radioinduced sequelae as pneumonitis and pulmonary fibrosis. It is known that exercise promotes a sequence of release of proinflammatory cytokines, decreasing the deleterious effects of cardiovascular disorders and promotion of protective effect against diseases associated with systemic inflammation. Given this fact, this study aimed to determine whether physical activity pre-radiotherapy has radioprotective elements by measuring the activation of proinflammatory cytokines such as interleukin-6 (IL-6), transforming growth factor-beta (TGF-'beta'), tumor necrosis factor-alpha (TNF-'alpha') and beta protein kinase (IKK'beta') by means of Western Blotting (WB) analysis. For this, we performed a randomized study using 28 male Wistar Hannover rats, males with a mean age of 90 days and and weighing approximately 200 grams. The animals were divided into 3 groups. Gl (control group), Gil (group underwent radiotherapy and sacrificed on day 1 after radiation therapy - Gila or sacrificed on day 7 post-radiotherapy -Glib) and GIN (the group that performed physical activity and radiotherapy and was sacrificed on day 1 post-radiotherapy-Gllla or sacrificed on day 7 post-radiotherapy-Glllb). The physical activity of the group GIN consisted of swimming for 8 weeks (zero load, three times per week, about 30 minutes). After this activity, Gil and GIN were subjected to irradiation by cobalt, a single dose of 3.5 Gy of whole body. All animals were sacrificed by an overdose of pentobarbital, according to the analysis time of cytokines, and then a fragment of the lower lobe of right lung was analyzed by WB. As a result, the expression of cytokines IKK 'beta', TNF-'alpha' and IL-6 induced by radiation in the lungs was lower in the exercised animals and that were sacrificed on day 7 post-radiotherapy (Glllb), with statistical significance by ANOVA test (p<0,05) . However, the exercise did not affect the increase induced by radiation in relation to TGF-'beta'. It was concluded that physical activity has radioprotective elements because there was a lower increase of IKK 'beta', TNF-'alpha' and IL-6 in post-exercise groups (Glllb), with suggestion of less inflammation and tissue injury after radiation therapy. Possibly there was no statistical significance in relation to TGF-'beta', as this cytokine plays an important role in a later phase of tissue injury, namely pulmonary fibrosis. Furthermore, the cytokines analyzed proved to be good markers to measure the pulmonary inflammatory response / Doutorado / Fisiopatologia Cirúrgica / Doutor em Ciências