RESUMO
Background: In current literature there are only scarce data on the host inflammatory response during Burkholderia cepacia complex (Bcc) persistence. The primary objective of the present research was to carry out cross-sectional analyses of biomarkers and evaluate disease progression in cystic fibrosis (CF) patients with chronic Bcc infection and pathogen-free ones. The secondary aim was to assess prospectively overall survival of the study participants during up to 8 years of follow-up. Methods: The study included 116 paediatric patients with CF; 47 CF patients were chronically infected with Bcc, and 69 individuals were Bcc free. Plasma and sputum biomarkers (neutrophil elastase, MMP-8, MMP-9, MMP-12, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-22, IL-23, IL-17, IFN-γ, TGFß1, TNF-α) were analysed using commercially available kits. Besides, inhibitory effect of dexamethasone on proliferative response of PHA-stimulated peripheral blood lymphocytes had been assessed. Results: Bcc infected patients did not differ from Bcc free ones in demographic and clinical parameters, but demonstrated an increased rate of glucose metabolism disturbances and survival disadvantage during prolong follow-up period. Biomarkers analyses revealed elevated TNF-α and reduced IL-17F levels in sputum samples of Bcc infected patients. These patients also demonstrated improvement of peripheral blood lymphocyte sensitivity to steroid treatment and reduction in plasma pro-inflammatory (IL-17F and IL-18) and anti-inflammatory (TGFß1 and IL-10) cytokine concentrations. Conclusions: Reduction in IL-17F levels may have several important consequences including increase in steroid sensitivity and glycemic control disturbances. Further investigations are needed to clarify the role of IL-17 cytokines in CF complication development. Low plasma TGFß1 and IL-10 levels in Bcc infected group may be a sign of subverted activity of regulatory T cells. Such immune alterations may be one of the factors contributing to the development of the cepacia syndrome.
Assuntos
Biomarcadores , Infecções por Burkholderia , Fibrose Cística , Citocinas , Humanos , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Fibrose Cística/mortalidade , Criança , Masculino , Feminino , Adolescente , Biomarcadores/sangue , Infecções por Burkholderia/mortalidade , Infecções por Burkholderia/imunologia , Estudos Transversais , Citocinas/sangue , Citocinas/metabolismo , Escarro/microbiologia , Pré-Escolar , Estudos Prospectivos , Progressão da Doença , Burkholderia cepacia , Complexo Burkholderia cepaciaRESUMO
BACKGROUND: Autism spectrum disorders (ASD) are known to be associated with an inflammatory process related to immune system dysfunction. This study's aim was to investigate the role of cell-free DNA in chronic inflammatory process in ASD patients. METHODS: The study included 133 ASD patients and 27 healthy controls. Sixty-two ASD patients were demonstrated to have mild-to-moderate disease severity (group I) and 71 individuals to have severe ASD (group II). Plasma cell-free (cf) DNA characteristics, plasma cytokine concentrations, expression of the genes for NFкB1 transcription factor and pro-inflammatory cytokines TNFα, IL-1ß and IL-8 in peripheral blood lymphocytes (PBL) of ASD patients, and unaffected controls were investigated. Additionally, in vitro experiments with oxidized DNA supplementation to PBL cultures derived from ASD patients and healthy controls were performed. RESULTS: The data indicates that ASD patients have demonstrated increased cfDNA concentration in their circulation. cfDNA of patients with severe ASD has been characterized by a high abundance of oxidative modification. Furthermore, ASD patients of both groups have shown elevated plasma cytokine (IL-1ß, IL-8, IL-17A) levels and heightened expression of genes for NFкB1 nuclear factor and pro-inflammatory cytokines TNFα, IL-1ß, and IL-8 in PBL. In vitro experiments have shown that NF-κB/cytokine mRNA expression profiles of ASD patient PBL treated with oxidized DNA fragments were significantly different from those of healthy controls. CONCLUSIONS: It may be proposed that oxidized cfDNA plays a role of stress-signaling factor activating the chronic inflammatory process in patients with ASD.
Assuntos
Transtorno do Espectro Autista/sangue , Ácidos Nucleicos Livres/sangue , Mediadores da Inflamação/sangue , Estresse Oxidativo/fisiologia , Transtorno do Espectro Autista/imunologia , Biomarcadores/sangue , Ácidos Nucleicos Livres/imunologia , Células Cultivadas , Criança , Pré-Escolar , Fragmentação do DNA , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , MasculinoRESUMO
BACKGROUND: Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. METHODS: The study included 204 patients with CF and 100 healthy controls; 102 CF patients were treated with basic therapy only (without anti-inflammatory treatment; WAT), and 102 individuals received basic therapy along with azithromycin (n = 59) or low-dose prednisolone (n = 43). The median duration of therapy was 24 months (range 12-82) with azithromycin and 31 months (range 12-180) with prednisolone. A cross-sectional analysis of plasma and sputum biomarkers was performed. RESULTS: Compared with the healthy controls, the WAT group showed elevated IFN-γ, IL-10 (total), and TGFß1 concentrations, and decreased TNFα (total) and adrenocorticotropic hormone (ACTH) levels (all p < 0.05). Plasma TNFα (total) concentrations in azithromycin/prednisolone patients were significantly higher than those in WAT patients and similar to those of healthy children. In contrast, IL-10 (total) levels were significantly decreased in azithromycin/prednisolone-treated patients compared with WAT patients. Children from the azithromycin group demonstrated ACTH levels similar to those of healthy controls. Azithromycin-treated patients showed a significantly reduced rate of CF-related liver disease and a significantly increased incidence of glucose metabolism disturbances. CONCLUSIONS: Steady-state anti-inflammatory treatments may have a sustained immunomodulatory action at systemic and local levels in CF patients. Further investigations are needed to assess the effects of supportive azithromycin therapy on the hypothalamic-pituitary-adrenal axis and the incidence of non-pulmonary CF complications.
Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Azitromicina/uso terapêutico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/patologia , Progressão da Doença , Prednisolona/uso terapêutico , Adolescente , Hormônio Adrenocorticotrópico/sangue , Biomarcadores/sangue , Criança , Estudos Transversais , Fibrose Cística/imunologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Genótipo , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Interferon gama/sangue , Interleucina-10/sangue , Elastase de Leucócito/sangue , Masculino , Fator de Crescimento Transformador alfa/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
BACKGROUND: Rosacea is a common, chronic, and inflammatory skin disease. The burden imposed by this condition requires that new topical treatments be sought to enlarge the arsenal of drugs available in order to better manage this disease. OBJECTIVES: This study was conducted to carry out an in vitro/in vivo evaluation of the antimicrobial activity of 3% praziquantel (PZQ) ointment and to determine its efficacy and safety in the treatment of rosacea. METHODS: Patients with rosacea (n = 65) participated in a 16-week, randomized, single-blind pilot study of the effects of twice-daily monotherapy with 3% PZQ ointment vs. placebo (vehicle ointment). Efficacy was assessed clinically using the Investigator's Global Assessment Scale (IGAS) and the Clinical Erythema Assessment Scale (CEAS). Patients' quality of life was also determined using the Dermatology Life Quality Index (DLQI). The antimicrobial potential of 3% PZQ ointment was assessed by agar diffusion assay. RESULTS: Scores on the IGAS and CEAS showed PZQ ointment to have a statistically significant therapeutic advantage over the placebo treatment (P < 0.001). At week 16, the PZQ group demonstrated a statistically significant greater reduction in CEAS score than the placebo group (P < 0.001). Analysis of CEAS scores showed that 41.9% of patients in the PZQ group and 18.2% of those in the placebo group achieved a CEAS score equivalent to a rating of "none". Mean scores on the DLQI at baseline and at the end of the study were, respectively, 15.8 and 4.1 in the praziquantel group. The PZQ-treated group also experienced a statistically significant improvement in comparison with the placebo group at week 16 (P < 0.001). The inhibitory zone indicating the extent of antimicrobial activity of 3% PZQ ointment ranged from 6 mm to 17 mm. No serious treatment-related adverse events occurred in either treatment group. CONCLUSIONS: Use of 3% PZQ ointment twice daily for 12 weeks resulted in significantly better effects than a placebo treatment in improving rosacea and the patient's quality of life.
Assuntos
Praziquantel/administração & dosagem , Rosácea/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Projetos Piloto , Método Simples-CegoRESUMO
BACKGROUND AND AIM: Macrolide antibiotics are widely used in the treatment of suppurative lung diseases including cystic fibrosis (CF), the most common inherited fatal disease in the Caucasian population. This condition is characterized by secondary Pseudomonas infection resulting in neutrophil infiltration within the airways. The aim of the study was to investigate the evolution of inflammatory process in CF patients receiving long-term clarithromycin therapy. METHODS: Twenty-seven CF patients (mean age, 12 years) were enrolled into the study. Beside the basic therapy the patients were treated with clarithromycin at a dose of 250 mg every other day orally. All patients were routinely examined every 3 months. Blood and sputum were collected before clarithromycin treatment and then again 3, 6 and 12 months after the drug prescription. Cytokine concentrations (tumor necrosis factor-alpha, interleukin-8, interleukin-4, interferon-gamma) in the sputum and plasma were assayed. Peripheral blood lymphocyte response to phytohemagglutinin was also evaluated. RESULTS: Clarithromycin treatment resulted in a marked reduction of the cytokine levels both in the sputum and plasma specimens. At the same time, the interferon-gamma/interleukin-4 ratio has been significantly elevated. In addition, a sustained increase of peripheral blood lymphocyte response to phytohemagglutinin was demonstrated. These changes were associated with a significant improvement of the lung function. CONCLUSIONS: The beneficial effect of the prolonged treatment of CF patients with a 14-membered ring macrolide antibiotic clarithromycin seems to be associated not only with down-regulation of the inflammatory response, but also with immunological changes including the switch from Th2 to Th1 type response.