RESUMEN
BACKGROUND: The balance between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-alpha contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-alpha is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators. AIMS: In the present study, the relationships between TNF-alpha and IL-10 in the plasma of healthy school-children and cystic fibrosis (CF) patients have been investigated. METHODS: Blood samples were obtained from 12 CF patients with chronic pulmonary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-alpha were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-alpha over anti-inflammatory IL-10 (TNF-alpha/IL-10 > 1). In these subjects, a significant positive linear association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-alpha/IL-10 ratios. In addition, a disappearance of correlation between the cytokine values was observed. Such disturbance was related to exuberant elevation of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma cytokine values remained in strong linear association independently of TNF-alpha or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients during a 6-month observation period have been revealed. CONCLUSIONS: There were no fundamental differences between CF and healthy children in the regulation of TNF-alpha and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-alpha, whereas immune disturbance was characterized by IL-10 superiority. The only abnormality that was found in CF patients consisted of their inability to produce unlimitedly IL-10 in response to antigen stimuli.
Asunto(s)
Fibrosis Quística/inmunología , Interleucina-10/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Adolescente , Niño , Humanos , Estadística como Asunto , Factores de Tiempo , VacunaciónRESUMEN
BACKGROUND: The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the pulmonary disease severity and progress. Malnutrition may be an important complicating factor in active and chronic lung disease. AIMS: The focus of this study was to investigate several inflammatory markers in pancreatic-insufficient CF patients with different enzyme treatment regimens. METHODS: CF patients with pancreatic insufficiency were examined at a time of symptomatic exacerbation of their lung disease. Group A (n = 11) regularly received microspheric enzymes. Group B (n = 8) were treated with enzymes during the hospitalization period only and demonstrated the presence of malnutrition. Inflammatory markers in the sputa (neutrophil elastase activity, interleukin-8 and tumour necrosis factor-alpha levels) and in the peripheral blood (plasma malondialdehyde (MDA), lymphocyte response to PHA, and the cell sensitivity to steroid suppression) have been investigated. RESULTS: During acute lung exacerbation, group B demonstrated reduced levels of lymphocyte proliferation. This parameter was normalized after combined antibiotic and pancreatic enzyme therapy. Simultaneously, plasma MDA in group B markedly increased following treatment. For this group, a significant positive linear association between values of plasma MDA and lymphocyte proliferation has been observed. For group A, neither the same correlation nor changes in MDA levels and lymphocyte proliferation have been found. CONCLUSIONS: Our data indicate that acute lung exacerbation in malnourished CF patients may be associated with alteration in T-lymphocyte activity. Adequate therapy normalizes lymphocyte function but results in systemic oxidative stress.
Asunto(s)
Fibrosis Quística/metabolismo , Trastornos Nutricionales/metabolismo , Estrés Oxidativo , Absorción , Adolescente , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/inmunología , Fibrosis Quística/terapia , Femenino , Humanos , Activación de Linfocitos , Masculino , Malondialdehído/sangre , Trastornos Nutricionales/complicacionesRESUMEN
Chronic endobronchial inflammation and bacterial infection are the main causes of morbidity and mortality in cystic fibrosis (CF), an autosomal recessive genetic disorder associated with improper function of chloride channels. Inflammation in CF lung is greatly amplified after Pseudomonas aeruginosa infection. In this study the relationship between P. aeruginosa status and inflammatory markers has been investigated. Seventeen CF children in acute lung exacerbation were examined. CF patients without P. aeruginosa infection were characterized by elevated activity of sputum elastase, reduced response of peripheral blood lymphocytes to PHA and significant resistance to the antiproliferative action of glucocorticoids. These parameters were normalized after antibiotic treatment. The patients with prolonged P. aeruginosa infection demonstrated extremely high levels of elastase activity and elevated amounts of sputum IL-8 and TNF-alpha. Although antibiotic treatment resulted in clinical improvement, it failed to suppress excessive immune response in the lung. The data indicate that CF patients with prolonged P. aeruginosa need the modified treatment, which should include immunomodulating drugs and protease inhibitors as well as antibacterial therapy.
Asunto(s)
Fibrosis Quística/complicaciones , Enfermedades Pulmonares/microbiología , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/fisiopatología , Antibacterianos/uso terapéutico , Células Cultivadas , Niño , Fibrosis Quística/fisiopatología , Dexametasona/farmacología , Humanos , Inflamación , Interleucina-8/análisis , Elastasa de Leucocito/análisis , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/fisiopatología , Activación de Linfocitos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Fitohemaglutininas , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Esputo/química , Factor de Necrosis Tumoral alfa/análisis , Capacidad VitalRESUMEN
Immunomodulating effects of a neoglycoconjugate created on the basis of alpha1-acid glycoprotein (AGP) carbohydrate chains and synthetic protein-free carrier have been investigated. It was demonstrated that this pseudo-AGP suppressed PHA- or anti-CD3 antibody-induced lymphocyte proliferation in a dose-dependent manner. Pseudo-AGP revealed a similar antiproliferative effect as the natural AGP samples. Stimulation of the LPS-induced proinflammatory cytokine production by mononuclear cells treated with both natural and pseudo-AGP has been also demonstrated. These data show that carbohydrate chains of AGP play a crucial role in the studied biological effect realization.