Interleukin-2 receptor β chain as a possible target for low doses of mafosfamide

The 7-day cytotoxic lymphocytes (CTL) induced in mixed lymphocyte culture express only the chain of the interleukin-2 receptor (IL-2R). In the present study this fact has been confirmed in a murine semi-allogeneic system. The ability of low doses of mafosfamide (Mf) to affect IL-2-induced CTL proliferation has been demonstrated. It was also shown that IL-2 activated resting suppressor cells. The pretreatment of the suppressor cells with either monoclonal antibodies (mAbs) against the p75 chain of IL-2R, or with Mf abolished the suppressive effect of these cells. No restoration of the proliferative response occurred when the anti-IL-2Rα mAb had been used. Flow cytometry analysis of 7-day CTL was carried out with mAbs against the α and β chains of IL-2R. CTL treatment with Mf inhibited anti-IL-2Rβ mAb binding. It may be assumed that the anti-proliferative effects of Mf which have been demonstrated in this paper, were a result of blocking the IL-2R β chain

Agrotechnology for Snapshots Soil Health with Bacteria

Taxonomic structure of bacterial microbiome of sod-podzolic soil (Gatchina district of Leningrad region, Russia) with varying degrees of moisture were studied using pyrosequencing of 16sRNA gene. Proteobacteria were revealed mostly in drought conditions and may be used as indicator microorganisms. The fractal analysis of the data showed that the index of the biosystem determinism of the frequencies of soil microbial communities decreased with drought (from 0.73 to 0.65), since decreases the number of variations of taxonomic units, due to which a smaller number of biosystem groups were formed

Anti-inflammatory and immunomodulating effects of clarithromycin in patients with cystic fibrosis lung disease.

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

Improvement of nutrient absorption may enhance systemic oxidative stress in cystic fibrosis patients.

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

Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection.

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

Маркеры воспаления у больных муковисцидозом

Inflammatory markers dynamics in 75 cystic fibrosis (CF) patients during a treatment of lung disease exacerbation has been investigated. As a rule, a clinical improvement is associated with decrease in the tumor necrosis factor-alpha and interleukin-8 levels in the sputum specimens. The neutrophil elastase (NE) activity assay is of special interest. It is the single inflammatory marker, which reflects the disease severity. Thus, CF patients with relatively good lung function (FVC and FEV1>70%) demonstrated lower NE activity. In contrast, the subjects with poor lung function (FVC and FEV1<70%) show the higher NE activity in the sputa. Though successful antibacterial therapy usually resulted in a decrease in the sputum elastase activity some severe CF patients demonstrate its elevation. This paradoxical result may be associated with neutrophil death and NE deliberation in the CF lung. It is very difficult to find the signs of systemic inflammation in peripheral blood of CF patients. However, our experience shows that the change of the peripheral blood lymphocytes sensitivity to the corticosteroid (dexamethasone) antiproliferative effect can inform a physician about the inflammatory process activation and an antibacterial treatment efficacy. Malon dialdehyde (MDA) plasma concentration is another parameter, which can show paradoxical results in CF subjects. During acute lung exacerbation some patients who were treated with enzymes during hospitalization period only in spite of the pancreatic insufficiency demonstrated marked increase in plasma MDA level. Authors postulate that such the increase does not reflect the activation of the infection but resuits from the systemic oxidative stress. The latter is a consequence of the improvement in fat absorption and of increase in the number of free radical targets.Исследование динамики маркеров воспаления у 75 больных муковисцидозом (MB) показало, что клиническое улучшение, как правило, сопровождалось снижением в мокроте концентрации фактора некроза опухолей-а и интерлейкина-8. Особый интерес представляет исследование активности нейтрофильной эластазы (НЭ), поскольку это единственный показатель, отражающий тяжесть течения заболевания. Так, у больных с относительно сохранной функцией легких (ФЖЕЛ и ОФВ1>70%) обнаруживалась и более низкая активность эластазы в мокроте. У больных с худшими показателями внешнего дыхания (ФЖЕЛ и ОФВ1<70%) активность эластазы в мокроте была выше. Хотя успешная антибактериальная терапия обычно приводила к заметному снижению активности НЭ, у некоторых больных с тяжелым течением MB данный показатель повышался. Этот парадоксальный результат может быть связан с массовой гибелью нейтррфилов в легких и освобождением НЭ. Несмотря на то что у больных MB в периферической крови трудно обнаружить признаки воспаления, исследование чувствительности лимфоцитов к антипролиферативному действию дексаметазона может дать объективную информацию о состоянии очага воспаления и эффективности антибактериальной терапии. Еще одним параметром, измерение которого у больных МВ может давать парадоксальные результаты, является уровень малонового диальдегида (МДА) в плазме. У группы больных наблюдалось повышение уровня МДА на фоне интенсивной антибактериальной терапии. Больные этой группы, несмотря на выраженную недостаточность экскреторной функции поджелудочной железы, начинали получать заместительную терапию только в стационаре. Авторы полагают, что повышение уровня МДА не связано  с обострением инфекционного процесса, а является свидетельством развития оксидативного стресса, так как улучшение всасывания жиров, связанное с назначением ферментов, ведет к резкому увеличению числа мишеней для свободных радикалов