Recent advances in the field of host immunity against parasitic nematodes have revealed the importance of macrophages in trapping tissue migratory larvae. Protective immune mechanisms against the rodent hookworm Nippostrongylus brasiliensis (Nb) are mediated, at least in part, by IL-4-activated macrophages that bind and trap larvae in the lung. However, it is still not clear how host macrophages recognize the parasite. An in vitro co-culture system of bone marrow-derived macrophages and Nb infective larvae was utilized to screen for the possible ligand-receptor pair involved in macrophage attack of larvae. Competitive binding assays revealed an important role for β-glucan recognition in the process. We further identified a role for CD11b and the non-classical pattern recognition receptor ephrin-A2 (EphA2), but not the highly expressed β-glucan dectin-1 receptor, in this process of recognition. This work raises the possibility that parasitic nematodes synthesize β-glucans and it identifies CD11b and ephrin-A2 as important pattern recognition receptors involved in the host recognition of these evolutionary old pathogens. To our knowledge, this is the first time that EphA2 has been implicated in immune responses to a helminth.

Previous studies have demonstrated that the interaction of CD40 on monocytes with CD40 ligand, present on activated CD4+ T cells, induces monocyte inflammatory cytokine synthesis and rescues monocytes from apoptosis. These findings suggest a role for CD40 signaling of monocyte activation in the maintenance and/or exacerbation of nonseptic (e.g., autoimmune) inflammatory responses. In the present study the effects of the modulatory cytokines IL-4 and IL-10 on CD40-mediated signaling of monocyte IL-1beta synthesis and rescue from apoptosis were examined. Both IL-4 and IL-10 decreased CD40-dependent IL-1beta synthesis in a dose-dependent manner individually and synergized in this effect when used concurrently, with minimal effect on CD40 surface expression. CD40 signaling of IL-1beta synthesis was shown to be dependent on the induction of protein tyrosine kinase (PTK) activity, and both IL-4 and IL-10 diminished CD40-mediated tyrosine phosphorylation of monocyte cellular proteins. However, IL-4, but not IL-10, blocked CD40-mediated rescue from apoptosis, an event that we have demonstrated previously to be dependent on PTK activity as well. Together these results suggest that in monocytes 1) both IL-4 and IL-10 target CD40-induced PTK activity in the down-regulation of IL-1beta synthesis; and 2) IL-4 and IL-10 have divergent effects on the CD40 signaling pathway, in that these cytokines are synergistic with respect to their abilities to inhibit CD40-mediated IL-1beta synthesis and differ in their abilities to block CD40-mediated rescue from apoptosis.

<p><strong>Rationale: </strong>Lung-homing of bone marrow (BM)-derived progenitor cells is associated with inflammatory and remodeling changes in asthma. Stromal cell derived factor-1α (SDF-1α) is a potent progenitor cell chemoattractant and its local production in the lung promotes lung homing of progenitor cells. The role of pro-inflammatory cytokines in promoting traffic of progenitor cells to the site of inflammation in asthma has not been investigated. The TH2 cytokines, interleukin (IL)-4 and IL-13, are key regulators of asthma pathology.</p> <p><strong>Objective: </strong>To investigate the role of IL-4 and IL-13 in modulating the trans-migrational responses of hemopoietic progenitor cells (HPC).</p> <p><strong>Methods: </strong>HPC were isolated from cord blood (CB) and peripheral blood (PB) and migrational and adhesive responses were assessed using transwell migration assays and adhesion to fibronectin-coated wells, respectively. Responding cells were enumerated by flow cytometry.</p> <p><strong>Results: </strong>IL-4 and IL-13 had no direct effect on progenitor cell migration. Pre-incubation with each of these cytokines primed SDF-1α stimulated migration of CB and PB-derived HPC (CD34+45+ cells) but not eosinophil-lineage committed progenitors (CD34+45+IL- 5Rα+ cells) or mature eosinophils to SDF-1α. For HPC, priming effects of IL-4 (0.1ng/ml) and IL-13 (0.1ng/ml) were detectable within 1hr and optimal at 18hr post- incubation and IL-4 was the more effective priming agent. Disruption of lipid rafts inhibited IL-4 priming of SDF-1α stimulated migration of HPC indicating that increased incorporation of CXCR4 into membrane lipid rafts mediates the cytokine primed migrational response of HPC. This was confirmed by confocal fluorescent microscopy.</p> <p><strong>Conclusions: </strong>IL-4 and IL-13 prime the migrational response of HPC to SDF-1α by enhancing the incorporation of CXCR4 into lipid rafts. The priming effect of these cytokines is specific to primitive HPC. These data suggest that increased local production of IL-4 and IL-13 within the lungs may promote increased SDF-1α mediated homing of BM-derived HPC to the airways in asthma.</p> / Master of Science in Medical Sciences (MSMS)

O Diabetes Mellitus tipo 1 (DM1A) é uma doença autoimune caracterizada pela infiltração pancreática de linfócitos T e B, macrófagos e células dendríticas, levando à perda progressiva da capacidade de secreção de insulina pelas células beta pancreáticas. A homeostase das células T, ou seja, o desenvolvimento e manutenção apropriados dos números e funções das células T são essenciais para a integridade do sistema imune. Classicamente acreditava-se que as células T CD4+ poderiam se subdividir em duas populações efetoras distintas, T helper 1 e T helper 2. Recentemente, foram descritas duas novas vias de ativação de linfócitos T CD4+: a via Th17, que tem papel fundamental na autoimunidade; a via T regulatória, onde células T CD4+CD25+ high são essenciais na tolerância periférica e proteção contra autoimunidade. As Interleucinas (IL) de cadeia gama comum agem em várias etapas desta diferenciação linfocítica. A IL-21 é o membro mais recente desta família de citocinas, que inclui também: IL-2, IL-4, IL-7 , IL-9 e IL-15. A IL-21 atua através da interação com seu receptor, o IL-21R, apresentando ações pleiotrópicas e, como regra, pró-inflamatórias. Em estudos com modelos animais de diabetes autoimune verificou-se que a IL-21 e seu receptor são essenciais para o desenvolvimento da doença, porém ainda não há estudos sobre a ação desta interleucina no DM1 em humanos. O objetivo de nosso estudo foi avaliar o papel dos receptores das interleucinas de cadeia gama comum na patogênese do DM1A através da determinação da expressão da proteína de superfície e do RNA mensageiro destes receptores em pacientes com DM1A de início recente, em comparação com indivíduos controles normais, e da correlação destes valores com títulos de autoanticorpos pancreáticos. Estudamos a expressão da proteína de superfície do IL-21R, IL-2R (CD25), IL-2R (CD122), IL-4R (CD124) e IL-7R (CD127) em linfócitos T periféricos de 35 pacientes com DM1 e 25 controles sadios utilizando citometria de fluxo. O tempo médio de diagnóstico do DM1 foi de 3 meses, e todos os pacientes estavam em uso de insulina no momento da coleta de sangue. Auto-anticorpos pancreáticos (anti-GAD65 e anti-IA2) foram dosados através de radioimunoensaio. A expressão do RNAm de IL-21R, IL-2R e IL-2R foi quantificada por PCR em tempo real em 23 dos pacientes portadores de DM1A. Detectamos, pela primeira vez, diminuição significativa na expressão proporcional de IL-21R, CD25 e CD122 em linfócitos TCD3+ e TCD4+, além de diminuição na expressão de CD124 em linfócitos T CD4+ e CD127 em linfócitos T CD3+. Verificamos também redução significativa na quantidade de células TCD4+CD25+high (T regulatórias) nos pacientes DM1A. Não houve correlação entre expressão dos receptores de superfície das interleucinas de cadeia gama comum e títulos de autoanticorpos pancreáticos. Realizamos o PCR em tempo real para quantificar a expressão do RNA mensageiro (RNAm) dos receptores de interleucinas de cadeia gama comum, e avaliar se esta correspondia à expressão das proteínas de superfície obtida através de citometria de fluxo. Comparamos a expressão do RNAm de IL-21R, IL-2R e IL-2R nos pacientes DM1A dividindo-os em tercis de acordo com os valores de expressão de proteína de superfície obtidos por citometria de fluxo em linfócitos T CD3+, e verificamos que não houve diferença entre os 3 grupos na expressão relativa dos genes estudados. Portanto, em nossa casuística a redução da expressão da proteína de superfície dos receptores de interleucinas de cadeia gama comum possivelmente decorreu de alterações posteriores à transcrição do RNA mensageiro / Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic infiltration of T and B lymphocytes, macrophages and dendritic cells, leading to a progressive destruction of the insulin-producing -cells. Homeostasis of T cells can be defined as the ability of the immune system to maintain normal T-cell counts and to restore T-cell numbers following T-cell depletion or expansion. It was classically believed that the CD4+ T cells could be activated into two distinct effector populations, T helper1 and T helper2. It was recently described two new pathways of CD4+ T lymphocytes activation: the Th17 pathway, that plays a fundamental role in autoimmunity and the regulatory pathway (Treg), where CD4+CD25+high T cells are essential to maintain peripheral tolerance and therefore protect against autoimmunity. The common gamma chain cytokines interfere with several steps of the CD4+ T lymphocytes differentiation. Interleukin-21 (IL-21) is the most recent member of this family, that also includes IL-2, IL-4, IL-7, IL-9 and IL-15, and has pleiotropic effects on the immune system. Interleukin-21 acts through interaction with its receptor, the IL-21R, which is expressed in a great variety of immune cells. Various studies with animal models of autoimmune diabetes demonstrated that IL-21 and its receptor are essential for the development of the disease, but there are no studies evaluating the role of this interleukin and its receptor in T1DM in humans. The aim of our study was to assess the role of common gamma chain-dependent cytokine receptors in the pathogenesis of T1D, by determining the expression of the surface protein and mRNA of these receptors in recent-onset T1D patients and correlating these values with titles of pancreatic autoantibodies. We studied the surface protein expression of IL-21R, IL-2R (CD25), IL-2R (CD122), IL-4R (CD124) and IL-7R (CD127) in peripheral T lymphocytes of 35 patients with T1D and 25 healthy controls using flow cytometry. Mean T1D duration was 3 months and all patients were using insulin at the time of blood withdraw. Pancreatic autoantibodies (anti-GAD65 and anti-IA2) were assessed by radioimmunoassay. The mRNA expression of IL-21R, IL-2R and IL-2R was quantified by real time PCR in 23 of the T1D patients. We detected for the first time a statistically significant decrease in the proportional expression of IL-21R, CD25 and CD122 on CD3+ and CD4+ T lymphocytes, a decrease in the expression of CD124 on CD4+ T cells and CD127 on CD3+ T lymphocytes. We also observed a significant reduction in the amount of CD4+ CD25+high (T regulatory cells) in T1D patients. There was no correlation between the expression of the surface receptors of common gamma chain cytokines and titles of pancreatic autoantibodies. We performed real-time PCR to quantify RNA expression of common gamma-chain interleukin receptors, and evaluate if these values corresponded to those of surface proteins obtained using flow cytometry. We compared the mRNA expression of IL-21R, IL-2R and IL-2R in T1D patients by dividing them into tertiles according to the expression values of surface protein obtained by flow cytometry in CD3+T lymphocytes. We observed that there was no difference in the relative expression of mRNA among the 3 groups of patients. Therefore, in our study, the reduction of surface protein expression of common gamma chain cytokines receptors was possibly due to alterations that occurred after the transcription of mRNA

Les interactions protéine - protéine sont au centre de nombreux processus biologiques, et représentent des cibles thérapeutiques pertinentes pour le traitement de certaines maladies. La conception de molécules antagonistes visant à inhiber ces interactions requiert la reconnaissance spécifique d’une des surfaces protéiques impliquées. Les foldamères de type oligoamides de quinoline constituent de bons candidats. Leur production et leur fonctionnalisation sont relativement aisées. Ils adoptent des structures hélicoïdales semblables à celles rencontrées dans les protéines. Grâce à différentes techniques biophysiques (CD, SPR, diffraction des rayons X), nous montrons que ces molécules sont aptes à reconnaître une surface protéique. Deux protéines cibles ont été choisies : l’interleukine 4 et l’anhydrase carbonique humaine II.La stratégie retenue dans ce travail (ancrage du foldamère à la protéine via un bras espaceur) nous a permis d’obtenir des informations structurales sur les interactions foldamère – protéine avant toute optimisation de ces interactions. La première structure 3D d’un complexe foldamère de quinoline complexée à une protéine est décrite. / Protein-protein interactions are a central issue in biological processes and represent relevant therapeutic targets for the treatment of diseases. The design of antagonistic molecules directed towards the disruption of these interactions requires the specific recognition of protein surfaces. Quinoline oligoamide foldamers present all the properties to reach that point. They are easily synthesized and fold into helices (similar to α helices) which can be decorated. Thanks to biophysical studies (CD, SPR, RX diffraction), we demonstrate that these molecules are able to recognize protein surfaces. Two proteins have been studied: the human interleukin 4 and the human carbonic anhydrase II.The applied strategy (keeping the foldamer close to the protein surface via a linker) allowed us to gather structural information about foldamer protein interactions before any strong binding is established. The first crystal structure between a protein and an aromatic amide foldamer is reported.

Background: Uterine fibriod (UF) or leiomyoma is the most frequent benign tumour upon lower genital tract and represents the most frequent indication for hysterectomy. The aetiology remains still unknown. The genetic factors contributing for the development of UF are being intensively investigated. The aim of our study was to look for possible genetic markers which could be used as prognostic tools for evaluation of an increased risk for development of UF. Methods: The study group enrolled 102 patients diagnosed with UF and 145 healthy controls. Ultrasonographic examination of the pelvis was performed and a single blood sample was taken in all women. Histological verification followed the surgery in the patient group. The principal of the cytokine gene polymorphisms detection is based on PCR reaction with sequence-specific primers. Results: A large spectrum of Th1/Th2 cytokine gene polymorphisms in patients with uterine fibroid was compared with control group. The frequencies of the majority of tested cytokine gene SNP in the patient cohort were not statistically different from the cytokine SNP in the control group. However, an intriguing association between polymorphisms of the IL-4 gene promotor at positions -590 C/T and -33 C/T, and the risk of leiomyoma was observed. The CC genotype of IL-4 at position...

O Diabetes Mellitus tipo 1 (DM1A) é uma doença autoimune caracterizada pela infiltração pancreática de linfócitos T e B, macrófagos e células dendríticas, levando à perda progressiva da capacidade de secreção de insulina pelas células beta pancreáticas. A homeostase das células T, ou seja, o desenvolvimento e manutenção apropriados dos números e funções das células T são essenciais para a integridade do sistema imune. Classicamente acreditava-se que as células T CD4+ poderiam se subdividir em duas populações efetoras distintas, T helper 1 e T helper 2. Recentemente, foram descritas duas novas vias de ativação de linfócitos T CD4+: a via Th17, que tem papel fundamental na autoimunidade; a via T regulatória, onde células T CD4+CD25+ high são essenciais na tolerância periférica e proteção contra autoimunidade. As Interleucinas (IL) de cadeia gama comum agem em várias etapas desta diferenciação linfocítica. A IL-21 é o membro mais recente desta família de citocinas, que inclui também: IL-2, IL-4, IL-7 , IL-9 e IL-15. A IL-21 atua através da interação com seu receptor, o IL-21R, apresentando ações pleiotrópicas e, como regra, pró-inflamatórias. Em estudos com modelos animais de diabetes autoimune verificou-se que a IL-21 e seu receptor são essenciais para o desenvolvimento da doença, porém ainda não há estudos sobre a ação desta interleucina no DM1 em humanos. O objetivo de nosso estudo foi avaliar o papel dos receptores das interleucinas de cadeia gama comum na patogênese do DM1A através da determinação da expressão da proteína de superfície e do RNA mensageiro destes receptores em pacientes com DM1A de início recente, em comparação com indivíduos controles normais, e da correlação destes valores com títulos de autoanticorpos pancreáticos. Estudamos a expressão da proteína de superfície do IL-21R, IL-2R (CD25), IL-2R (CD122), IL-4R (CD124) e IL-7R (CD127) em linfócitos T periféricos de 35 pacientes com DM1 e 25 controles sadios utilizando citometria de fluxo. O tempo médio de diagnóstico do DM1 foi de 3 meses, e todos os pacientes estavam em uso de insulina no momento da coleta de sangue. Auto-anticorpos pancreáticos (anti-GAD65 e anti-IA2) foram dosados através de radioimunoensaio. A expressão do RNAm de IL-21R, IL-2R e IL-2R foi quantificada por PCR em tempo real em 23 dos pacientes portadores de DM1A. Detectamos, pela primeira vez, diminuição significativa na expressão proporcional de IL-21R, CD25 e CD122 em linfócitos TCD3+ e TCD4+, além de diminuição na expressão de CD124 em linfócitos T CD4+ e CD127 em linfócitos T CD3+. Verificamos também redução significativa na quantidade de células TCD4+CD25+high (T regulatórias) nos pacientes DM1A. Não houve correlação entre expressão dos receptores de superfície das interleucinas de cadeia gama comum e títulos de autoanticorpos pancreáticos. Realizamos o PCR em tempo real para quantificar a expressão do RNA mensageiro (RNAm) dos receptores de interleucinas de cadeia gama comum, e avaliar se esta correspondia à expressão das proteínas de superfície obtida através de citometria de fluxo. Comparamos a expressão do RNAm de IL-21R, IL-2R e IL-2R nos pacientes DM1A dividindo-os em tercis de acordo com os valores de expressão de proteína de superfície obtidos por citometria de fluxo em linfócitos T CD3+, e verificamos que não houve diferença entre os 3 grupos na expressão relativa dos genes estudados. Portanto, em nossa casuística a redução da expressão da proteína de superfície dos receptores de interleucinas de cadeia gama comum possivelmente decorreu de alterações posteriores à transcrição do RNA mensageiro / Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic infiltration of T and B lymphocytes, macrophages and dendritic cells, leading to a progressive destruction of the insulin-producing -cells. Homeostasis of T cells can be defined as the ability of the immune system to maintain normal T-cell counts and to restore T-cell numbers following T-cell depletion or expansion. It was classically believed that the CD4+ T cells could be activated into two distinct effector populations, T helper1 and T helper2. It was recently described two new pathways of CD4+ T lymphocytes activation: the Th17 pathway, that plays a fundamental role in autoimmunity and the regulatory pathway (Treg), where CD4+CD25+high T cells are essential to maintain peripheral tolerance and therefore protect against autoimmunity. The common gamma chain cytokines interfere with several steps of the CD4+ T lymphocytes differentiation. Interleukin-21 (IL-21) is the most recent member of this family, that also includes IL-2, IL-4, IL-7, IL-9 and IL-15, and has pleiotropic effects on the immune system. Interleukin-21 acts through interaction with its receptor, the IL-21R, which is expressed in a great variety of immune cells. Various studies with animal models of autoimmune diabetes demonstrated that IL-21 and its receptor are essential for the development of the disease, but there are no studies evaluating the role of this interleukin and its receptor in T1DM in humans. The aim of our study was to assess the role of common gamma chain-dependent cytokine receptors in the pathogenesis of T1D, by determining the expression of the surface protein and mRNA of these receptors in recent-onset T1D patients and correlating these values with titles of pancreatic autoantibodies. We studied the surface protein expression of IL-21R, IL-2R (CD25), IL-2R (CD122), IL-4R (CD124) and IL-7R (CD127) in peripheral T lymphocytes of 35 patients with T1D and 25 healthy controls using flow cytometry. Mean T1D duration was 3 months and all patients were using insulin at the time of blood withdraw. Pancreatic autoantibodies (anti-GAD65 and anti-IA2) were assessed by radioimmunoassay. The mRNA expression of IL-21R, IL-2R and IL-2R was quantified by real time PCR in 23 of the T1D patients. We detected for the first time a statistically significant decrease in the proportional expression of IL-21R, CD25 and CD122 on CD3+ and CD4+ T lymphocytes, a decrease in the expression of CD124 on CD4+ T cells and CD127 on CD3+ T lymphocytes. We also observed a significant reduction in the amount of CD4+ CD25+high (T regulatory cells) in T1D patients. There was no correlation between the expression of the surface receptors of common gamma chain cytokines and titles of pancreatic autoantibodies. We performed real-time PCR to quantify RNA expression of common gamma-chain interleukin receptors, and evaluate if these values corresponded to those of surface proteins obtained using flow cytometry. We compared the mRNA expression of IL-21R, IL-2R and IL-2R in T1D patients by dividing them into tertiles according to the expression values of surface protein obtained by flow cytometry in CD3+T lymphocytes. We observed that there was no difference in the relative expression of mRNA among the 3 groups of patients. Therefore, in our study, the reduction of surface protein expression of common gamma chain cytokines receptors was possibly due to alterations that occurred after the transcription of mRNA

Background: Uterine fibriod (UF) or leiomyoma is the most frequent benign tumour upon lower genital tract and represents the most frequent indication for hysterectomy. The aetiology remains still unknown. The genetic factors contributing for the development of UF are being intensively investigated. The aim of our study was to look for possible genetic markers which could be used as prognostic tools for evaluation of an increased risk for development of UF. Methods: The study group enrolled 102 patients diagnosed with UF and 145 healthy controls. Ultrasonographic examination of the pelvis was performed and a single blood sample was taken in all women. Histological verification followed the surgery in the patient group. The principal of the cytokine gene polymorphisms detection is based on PCR reaction with sequence-specific primers. Results: A large spectrum of Th1/Th2 cytokine gene polymorphisms in patients with uterine fibroid was compared with control group. The frequencies of the majority of tested cytokine gene SNP in the patient cohort were not statistically different from the cytokine SNP in the control group. However, an intriguing association between polymorphisms of the IL-4 gene promotor at positions -590 C/T and -33 C/T, and the risk of leiomyoma was observed. The CC genotype of IL-4 at position...

No description available.

Introdução: A rinite alérgica (RA) e a rinossinusite crônica (RSC) são doenças inflamatórias nasais com prevalência alta e crescente. Estima-se que 15,5% dos norte-americanos tenham RSC, e estudo recente encontrou prevalência de 5,51% na cidade de São Paulo, enquanto a RA acomete entre 10 e 20% da população mundial. Apesar de terem mecanismos fisiopatológicos distintos, em ambas, há recrutamento de células de defesa, principalmente linfócitos T, e produção de citocinas inflamatórias. Esses mediadores variam não apenas entre as doenças, mas também entre as populações acometidas, e seu conhecimento é importante para o diagnóstico correto e direcionamento da terapia escolhida. Objetivos: Mapear os mediadores inflamatórios presentes no lavado nasal e no condensado do ar exalado na RSC e na RA, avaliando possíveis biomarcadores da doença, e analisar o endotipo inflamatório dos pacientes estudados. Além disso, avaliar a qualidade de vida, o nível de obstrução nasal, a qualidade do sono dos pacientes afetados, o transporte mucociliar e coletar material para análise de pH, contagem de células totais e seu diferencial. Pacientes e métodos: Estudo exploratório prospectivo em corte transversal, sendo os pacientes divididos em quatro grupos: 1) Grupocontrole com pacientes sem queixas; 2) Pacientes com RA com prick test positivo; 3) Pacientes com RSC com polipose; e 4) Pacientes com RSC sem polipose. Todos os pacientes responderam a quatro questionários: 20-Item Sino-Nasal Outcome Test (SNOT-20p), Nasal Obstruction Symptom Evaluation (NOSE), o Índice de Qualidade do Sono de Pittsburgh (Pittsburgh Sleep Quality Index - PSQI-BR) e o questionário para triagem e diagnóstico da asma da European Community Respiratory Health Survey (ECRHS). Foi realizado exame físico, incluindo endoscopia nasal (escore de Lund- Kennedy modificado) e, nos pacientes com RSC, avaliação da tomografia computadorizada (TC) de face (escore de Lund-Mackay). Foi também avaliado o transporte mucociliar por meio do teste da sacarina. Coletou-se o condensado do ar exalado para análise do pH e lavado nasal para avaliação do pH, da presença de citocinas e da celularidade (total e diferencial). Foi avaliada a presença de IL-4, IL-5, IL-8, IL-17A, IL-22, TNF-Alfa e IFN-Gama no lavado nasal e IL-5, IL-17A, IL-22 e IFN-Gama no condensado do ar exalado. Resultados: Os pacientes com RSC apresentaram escores significativamente piores nos questionários de obstrução nasal (NOSE, p < 0,01) e qualidade de vida (SNOT-20p, p < 0,01) quando comparados aos controles, e tanto os pacientes com RSC quanto com RA apresentaram pior qualidade do sono (PSQI-BR, p < 0,01). O escore de extensão de Lund- Mackay foi mais elevado nos pacientes com RSC com polipose (p < 0,02). O teste da sacarina apresentou tempo mais prolongado no grupo RSC com polipose (p < 0,01). O pH do condensado do ar exalado não diferiu entre os grupos. O grupo RSC com polipose apresentou tanto diferença do pH (p < 0,01) quanto da contagem de células totais do lavado nasal (p < 0,01) quando comparado ao grupo-controle, porém sem diferença na contagem diferencial. IFN? do condensado foi mais elevado no grupo RA em comparação ao grupo C (p=0,05), enquanto IL-5 foi mais alto no grupo RSC com polipose quando comparado ao grupo RSC sem polipose (p=0,02). Os pacientes foram, então, divididos em endotipos, segundo os grupos descritos por Tomassen et al., sendo que endotipos são os subtipos da doença definidos funcionalmente e patologicamente por mecanismos moleculares distintos. Conclusão: Pacientes com RSC apresentaram escores piores nos questionários de qualidade de vida (SNOT-20p e NOSE), o que, em parte, poderia ser atribuído à pior qualidade do sono apresentada tanto por estes pacientes quanto pelos portadores de RA. O teste da sacarina evidenciou pior transporte mucociliar nos pacientes com RSC com polipose. Não houve diferença do pH do condensado do ar exalado, sugerindo que, apesar de interessante na avaliação das vias aéreas inferiores, este pode não ser um bom teste para análise das vias aéreas superiores. Foram encontradas alterações significantes tanto do pH quanto da contagem de células totais do lavado nasal do grupo com RSC com polipose, sem, no entanto, haver diferença na contagem diferencial. Dos 17 pacientes com RSC com perfil completo de citocinas, 12 se encaixam em endotipos já descritos, sendo que, dos cinco restantes, dois apresentam o mesmo perfil, podendo indicar um novo subgrupo / Introduction: Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are nasal inflammatory diseases with high and increasing prevalence. It is estimated that 15.5% of Americans have CRS, and a recent study found a prevalence of 5.51% in the city of São Paulo, while AR affects between 10 and 20% of the world population. Although they have distinct pathophysiological mechanisms, in both there is recruitment of defense cells, mainly T lymphocytes, and production of inflammatory cytokines. These mediators vary not only between diseases but also among affected populations, and their knowledge is important for the correct diagnosis and targeting of the therapy chosen. Objectives: To map the inflammatory mediators present in the nasal wash and the exhaled breath condensate in the CRS and AR, evaluating possible biomarkers of this diseases, and to analyze the inflammatory endotype of the patients studied. In addition, assess quality of life, level of nasal obstruction, sleep quality of affected patients, mucociliary transport and collect samples for pH analysis, total cell count and its differential. Patients and Methods: Prospective cross-sectional exploratory study, divided into four groups: 1) Control group with patients without complaints 2) Patients with AR with prick test positive 3) Patients with CRS with polyps 4) Patients with CRS without polyps. All patients responded to four questionnaires: 20-Item Sino-Nasal Outcome Test (SNOT-20p), Nasal Obstruction Symptom Evaluation (NOSE), Pittsburgh Sleep Quality Index (PSQI-BR) and European Community Respiratory Health Survey (ECRHS) questionnaire for screening and diagnosis of asthma. A physical examination was performed, including nasal endoscopy (modified Lund-Kennedy score) and, in patients with CRS, a computerized tomography (Lund-Mackay score) evaluation. The mucociliary transport was also evaluated through the saccharin test. The exhaled breath condensate was collected for pH analysis and the nasal wash for evaluation of pH, cytokines and cellularity (total and differential). The presence of IL-4, IL-5, IL-17, IL-17A, IL-22, TNF-Alfa and IFN-Gama in the nasal wash and IL-5, IL-17A, IL-22 and IFN-Gama in the exhaled breath condensate. Results: Patients with CRS had significantly worse scores in the nasal obstruction questionnaire (NOSE, p < 0.01) and quality of life questionnaire (SNOT-20p, p < 0.01) when compared to controls, and both patients with CRS and AR presented worse sleep quality (PSQI-BR, p < 0.01). The Lund-Mackay extension score was higher in patients with CRS with polyps (p < 0.02). The saccharin test showed longer time in the CSR group with polyps (p < 0.01). The pH of the exhaled breath condensate did not differ between groups. The CRS with polyps group presented both pH difference (p < 0.01) and higher total nasal wash cell count (p < 0.01) when compared to the control group, but with no difference in the differential count (p = 0.05), while IL-5 was higher in the CRS group with polyps when compared to the RSC without polyps group (p = 0.02). Patients were then divided into endotypes according to the groups described by Tomassen et al, Endotypes are the subtypes of the disease defined functionally and pathologically by distinct molecular mechanisms. Conclusions: Patients with CRS presented worse scores on quality of life questionnaires (SNOT-20p and NOSE), which could be attributed in part to the poorer quality of sleep presented by both patients with CRS and AR. The saccharin test evidenced worse mucociliary transport in patients with CRS with polyps when compared with control group. There was no difference in the pH of the exhaled breath condensate, suggesting that, although interesting in the evaluation of the lower airways, this may not be a good test for analyzing the upper airways. Significant alterations were found in both pH and total nasal wash cell count in the CSR group with polyposis, but there was no difference in the differential count. Of the 17 patients with CRS with complete cytokine profile, 12 fit into already described endotypes, and of the remaining five, two have the same profile, which may indicate a new subgroup