Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression.

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).

TNF gene polymorphisms in cystic fibrosis patients: contribution to the disease progression.

Background: It is well known that the disease progression in cystic fibrosis (CF) patients may be diverse in subjects with identical mutation in CFTR gene. It is quite possible that such heterogeneity is associated with TNF-α and/or LT-α gene polymorphisms since their products play a key role in inflammation. The aim of the study was to investigate the possible roles of TNF gene polymorphisms in CF disease phenotype and progression.

Cognitive disorders in mice: cytokine signaling pathways as therapeutic targets.

Surplus accumulation of regulatory T cells (Tregs) is known to be at the bottom of many morbid conditions, among them being neuropsychiatric diseases. In particular, Tregs may inhibit Th1 cells, including brain autoimmune lymphocytes, controlling the local microglial response and brain tissue homeostasis. The present study was undertaken in an attempt to suggest a novel approach for the treatment of maladaptation to mental stress associated with excessive Treg accumulation.

HPA axis exhaustion and regulatory T cell accumulation in patients with a functional somatic syndrome: recent view on the problem of Gulf War veterans.

The authors proceeded from the assumption that physical and mental symptoms of functional somatic syndromes (including those observed in Gulf War veterans) are based on both underactivity of hypothalamic-pituitary-adrenal (HPA) axis and excessive accumulation of regulatory T cells (Tregs). Permanent psychogenic stress coupled with high antigen loading leads to gradual depletion of HPA axis, which is manifested by the reduction of stress-induced cortisol response. Under stress hormone deficiency, Tregs begin to play a principal role in anti-inflammatory mechanisms and each new pro-inflammatory stimulus increases their number.

Melphalan reduces the severity of experimental colitis in mice by blocking tumor necrosis factor-alpha signaling pathway.

Melphalan is an alkylating agent, which is commonly used as an antineoplastic drug. Its cytostatic effect can be realized in humans in the dose range of 0.6-1.

Preventive and therapeutic effects of alpha-acid glycoprotein in mice infected with B. anthracis.

We studied the effects of alpha1-acid glycoprotein preparations on the survival rate of BALB/c mice infected with the lethal dose of B. anthracis STI-1. Apart from native alpha1-acid glycoprotein from donor blood, we studied 3 glycoforms differing in the affinity for concanavalin A and structure of carbohydrate chains.

Alkylating drugs applied in non-cytotoxic doses as a novel compounds targeting inflammatory signal pathway.

Alkylating drugs (ADs) belonging to the nitrogen mustard family are commonly used as cytostatic and immunosuppressive agents. Our previous in vitro studies demonstrated that in the case of gradual dose decrease, the number of targets for alkylation in the cell is also reduced and the drug switches from brutal cytostatic to cell growth modifier. At doses of 0.

Immunoglobulin G subclass profile of antimeasles response in vaccinated children and in adults with measles history.

The aim of this study was to investigate measles-specific immunoglobulin G (IgG) subclass profile in vaccinated children and in adults with natural infection. Serum samples were collected before and 30 days after vaccination. The sera from 51 late convalescent adults and seven adults with natural measles infection at the 12th day after onset of rash have been also investigated.

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.

Cytokine profile after rubella vaccine inoculation: evidence of the immunosuppressive effect of vaccination.

Background And Aim: Immunization with live virus vaccines may cause an immunosuppression with lymphopaenia, impaired cytokine production and defective lymphocyte response to mitogenes. These abnormalities were described in subjects vaccinated against measles. This study was performed to analyse the host immune response related to immunosuppression in subjects vaccinated with live attenuated rubella vaccine.

Tumor necrosis factor-alpha/interleukin-10 balance in normal and cystic fibrosis children.

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.

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.

Stimulatory and protective effects of alkylating agents applied in ultra-low concentrations.

Alkylating drugs belonging to the nitrogen mustard family are known as cytostatic and immunosuppressive agents. Ultra-low doses of these drugs may demonstrate pharmacological effects unlike this category of drugs. In the case of a gradual dose decrease, the number of targets for alkylation is also reduced and the drug switches from cytostatic to cell growth modifier.

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.

Immunomodulating activities of a natural alpha1-acid glycoprotein and its carbohydrate chains attached to the protein-free polymer.

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.

Changes in TNF and IL-6 production after diphtheria toxoid vaccination: drug modulation of the cytokine levels.

The effect of vaccination with diphtheria toxoid (AD-M) on TNF and IL-6 production has been studied in humans. In the present study it was demonstrated that immunization with AD-M resulted in changes of in vitro TNF and IL-6 production by peripheral blood mononuclear cells. TNF release was suppressed but IL-6 production was stimulated.

Interleukin-2 receptor beta 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.

Immunosuppressive action of cyclophosphamide in mice: contribution of some factors to determination of strain differences.

Mechanisms of strain differences in susceptibility to cyclophosphamide (CP) has been investigated with BALB/c, DBA/2, CC57BR, and C57BL/6 mice. It was shown that the final immunosuppressive effects of CP is a result of a combination of such factors as the level of CP alkylating metabolites in the bloodstream and the sensitivity of the target cells to antiproliferative action of these metabolites. The importance of the immune status peculiarities has been discussed.

Pharmacokinetics of alkylating metabolites of cyclophosphamide in different strains of mice.

Determination of the amount of alkylating (NBP) metabolites of cyclophosphamide (CP) in blood serum of BALB/c and DBA/2 mice has revealed that the shape of the curve describing the accumulation of NBP-metabolites, depends on the administered drug dose and animals' genotype. The experimental data obtained made it possible to suggest an improved pharmacokinetic model which takes into account a possible switching in of factors conditioning non-linear changes in the intensity of the accumulation processes in blood and elimination of CP alkylating metabolites from blood. The effect of different CP alkylating metabolite kinetics in BALB/c and DBA/2 mice on a different sensitivity of these mice to the immunodepressive action of CP in vivo, has been discussed.

Inhibition of phytohemagglutinin-induced lymphocyte proliferation by dexamethasone: mechanisms of individual susceptibility.

Direct positive correlation has been shown between the level of stimulation of peripheral blood lymphocytes and of the inhibition degree of PHA stimulation by dexamethasone. On the basis of this correlation we subdivided all the examined individuals into three groups of susceptibility: resistant, sensitive, and intermediate. The studies carried out in these groups showed that the reception effectiveness of glucocorticoids (GC) was much higher in the sensitive group than in the group of resistant individuals.