Urszula Demkow

Proinflammatory cytokines IL-6 and TNF-α and the development of inflammation in obese subjects

BackgroundThe development of obesity and related disorders, e.g., type II diabetes (T2D), hypertension, and metabolic disturbances is strongly related to increased levels in proinflammatory cytokines (IL-1, IL-6, and TNF-α). Both IL-6 and TNF-α are secreted by adipocytes and their concentration correlates with the percentage and distribution of fat tissue in the body. Both cytokines are the main factors responsible for the induction of acute phase proteins production (e.g., CRP) and to inflammatory state.ObjectiveTo compare of TNF-α and IL-6 concentrations in serum from obese subjects with those in subjects with normal BMI and to analyze the relation between TNF-α, IL-6, BMI and the inflammatory state as measured by the level of CRP.Material and methodsThe study included 80 obese subject (54 males and 26 females) BMI > 25 kg/m2. A control group consisted of 53 healthy subjects (24 males and 29 females) with BMI < 25 kg/m2. To determine the blood plasma concentration of IL-6 and TNF, commercial ELISA assay kits were used.ResultsThe concentration of IL-6 was lower in the control compared with the obese patients, but a significance difference concerned only female subjects (P = 0.001). TNF-α concentration was significantly higher in all obese subjects (P < 0.001). A higher level of this cytokine was also found in patients with obesity suffering from T2DM. A positive correlation was present between IL-6 and TNF-α concentrations. Only did the IL-6 level correlate with the concentration of CRP in serum.ConclusionsThe study confirmed that increased inflammatory cytokines lead to the persistence of inflammation in obese subjects. However, some other factors, such as gender, may contribute to the development of obesity-related inflammatory states.

Adiponectin as a biomarker of the metabolic syndrome in children and adolescents

The prevalence of obesity in children and adolescents has been increasing worldwide. As in adults, childhood obesity is closely related to hypertension, dyslipidemia, type 2 diabetes, and insulin resistance (IR) syndrome. Moreover, obese children have been found to be at increased risk of becoming obese adults. Obese children and adolescents tend to develop serious medical and psychosocial complications and also are at greater risk morbidity and mortality in adulthood. The molecular basis of the pathogenesis of obesity-linked disorders has not been fully elucidated. Adipose tissue serves not only as an energy storage organ, but also as an endocrine organ. It releases many factors with autocrine, paracrine and endocrine functions. Adipokines such as leptin, resistin, tumor necrosis factor-α, interleukin-6, adipsin, visfatin, and adiponectin are biologically active molecules produced by adipose tissue. They play a role in energy homeostasis, and in glucose and lipid metabolism. Adiponectin level, unlike that of other adipocytokines, is decreased in obesity and increased after weight reduction. Adiponectin has been associated with both central obesity and increased visceral adipose tissue and it has anti-inflammatory, anti-atherogenic, and potent insulin-sensitizing (anti-diabetic) effects.

Frequency and Activation of CD4+CD25high FoxP3+ Regulatory T Cells in Peripheral Blood from Children with Atopic Allergy

Background: Atopic allergy is among the immune tolerance-related disorders resulting from a failure of the regulatory network. Regulatory T cells (Tregs) play a leading role in the development of homeostasis in the immune system. The aim of this study was to determine the role of Tregs in the pathogenesis of atopic diseases in children by exploring the relationship between Treg frequency, activation markers and the clinical manifestations of the disease. Methods: Twenty allergic and 50 healthy children were enrolled to the study. Peripheral blood mononuclear cells were stained with monoclonal antibodies (anti-CD25-CD4-CD127-FoxP3-CD69-CD71) and evaluated using flow cytometry. Tregs were identified as CD4+CD25+/highFoxP3+CD127- T cells. Results: The percentage of Tregs in allergic patients (2.3%) was significantly decreased in comparison to healthy controls (4.6%, p = 0.003). The frequency of Tregs in patients with symptoms of atopic dermatitis and/or food allergy (1.7%) was significantly lower than in patients without these symptoms (2.9%, p = 0.04). A significant correlation between the percentage of Tregs and the sIgE serum concentration was observed (p = 0.037). Relative fluorescence intensities of FoxP3 expression in allergic patients were higher than in healthy controls (p = 0.00004). The frequency of CD4+CD25highCD127-CD71+ cells did not differ between the groups. Conclusions: Tregs display substantial deficiencies in atopic children, especially in children with multiorgan involvement, compared to patients with single organ manifestations. Additionally, there is an association between Tregs and the sIgE serum concentration. Better identification and characterization of Tregs in allergy is needed as they limit responses to foreign antigens, thereby minimizing T cell-mediated immunopathology in allergic diseases.

Brain inflammation and hypertension: the chicken or the egg?

Inflammation of forebrain and hindbrain nuclei controlling the sympathetic nervous system (SNS) outflow from the brain to the periphery represents an emerging concept of the pathogenesis of neurogenic hypertension. Angiotensin II (Ang-II) and prorenin were shown to increase production of reactive oxygen species and pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)) while simultaneously decreasing production of interleukin-10 (IL-10) in the paraventricular nucleus of the hypothalamus and the rostral ventral lateral medulla. Peripheral chronic inflammation and Ang-II activity seem to share a common central mechanism contributing to an increase in sympathetic neurogenic vasomotor tone and entailing neurogenic hypertension. Both hypertension and obesity facilitate the penetration of peripheral immune cells in the brain parenchyma. We suggest that renin-angiotensin-driven hypertension encompasses feedback and feedforward mechanisms in the development of neurogenic hypertension while low-intensity, chronic peripheral inflammation of any origin may serve as a model of a feedforward mechanism in this condition.

Neutrophils in asthma—A review

Asthma is a chronic inflammatory disease, with an array of cells involved in the pathogenesis of the disease. The role of neutrophils in the development of bronchial asthma is found to be complex, as they may trigger activation of immunocompetent cells and are a potent source of free oxygen radicals and enzymes participating in airway remodeling. The review highlights the role of neutrophils in bronchial asthma.

Neutrophils: The Role of Oxidative and Nitrosative Stress in Health and Disease

Neutrophils constitute the first line of the innate immunity in humans. They employ several strategies to trap and kill microorganisms, such as phagocytosis, degranulation, and the formation of extracellular traps (NETs). It has been well documented, that generation of reactive oxygen and nitrogen species (ROS and RNS) is crucial in the life cycle of a polymorphonuclear phagocyte. These compounds due to high reactivity act as powerful antimicrobial factors in the process of pathogens clearance and can also modulate immunological response. On the other hand, excessive amount of free radicals may have detrimental effect on host tissues and markers of oxidative and nitrosative stress are detectable in many diseases. It is necessary to maintain the balance between ROS/RNS formation and removal. The review highlights our current understanding of the role of ROS and RNS produced by neutrophils in health and disease.

Cross-talk between the inflammatory response, sympathetic activation and pulmonary infection in the ischemic stroke

The immune system response and inflammation play a key role in brain injury during and after a stroke. The acute immune response is responsible for secondary brain tissue damage immediately after the stroke, followed by immunosuppression due to sympathetic nervous system activation. The latter increases risk of infection complications, such as pneumonia. The pneumonia-related inflammatory state can release a bystander autoimmune response against central nervous system antigens, thereby initiating a vicious circle. The aim of this review is to summarize the relationship between ischemic stroke, sympathetic nervous system activation and pulmonary infection.

Role of elastases in the pathogenesis of chronic obstructive pulmonary disease: Implications for treatment

Neutrophil elastase, metalloproteinases, and their inhibitors play an important role in the development of chronic obstructive pulmonary disease (COPD), resulting in extensive tissue damage and malfunctioning of the airways. Nearly fifty years after the protease-antiprotease imbalance hypothesis has been suggested for the cause of emphysema, it is still appealing, but it does not explain the considerable variation in the clinical expressions of emphysema. However, there are many recent research findings to support the imbalance hypothesis as will be shown in this review. Although limited, there might be openings for the treatment of the disease.

Inhibitory capacity of different steroids on neutrophil migration across a bilayer of endothelial and bronchial epithelial cells

Neutrophil infiltration to the airway lumen is a common feature of respiratory inflammatory processes. The aim of this study was to evaluate whether different corticosteroids exert any selective effect on the migration of isolated neutrophils. A bilayer of cultured human endothelial and bronchial epithelial cells was used as a model for neutrophil migration through the blood-air barrier. Low spontaneous migration of neutrophils (2.8+/-0.9%, n=8; mean+/-S.E.M.) occurred, while in the absence of any steroid, a migration of 28.5+/-7.6% could be induced by lipopolysaccharide. Pre-incubation during 1 h of epithelial cells with dexamethasone, budesonide, or prednisolone (10(-10)-10(-4) M) showed in all instances a concentration-dependent inhibition following a bell-shaped curve. At 10(-7) M, both dexamethasone and budesonide were on the minimum effect peak of the bell-shaped curve. The peak for prednisolone was found at 10(-8) M. However, when steroid pre-incubation was extended to 4 h, a sigmoid curve was observed, with significant inhibition of migration at concentrations >10(-7) M. Steroids can inhibit neutrophil recruitment through two different pathways with distinct result, depending on the length of incubation time.

No association of LEPR Gln223Arg polymorphism with leptin, obesity or metabolic disturbances in children

ObjectiveThe aim of the study was to investigate whether the Gln223Arg in the leptin receptor may influence body weight, leptin concentration, and metabolic parameters in children.Materials and methodsThe examined group included 101 obese children (58 girls and 43 boys) with BMI 31.41 ± 5.03 kg/m2 (BMI ≥ 2 SDS) and the control group consisted of 41 children with BMI 20.0 ± 0.80 kg/m2 (BMI < 1.0 SDS). Polymorphism identification was performed in total genomic DNA using PCRRFLP method.ResultsThe distribution of genotypes LEPR was the following: in the obese group: AA - 20.8%, AG-55.4%, GG-23.8%; in the control group AA-31.7%, AG-53.65%, GG-14.65%. Comparative analyses between AA homozygous children and carriers of G alleles did not confirm any relation between the analyzed polymorphism and BMI, leptin concentrations, and metabolic disturbances in children with obesity.ConclusionIn children with obesity we did not observe association of the LEPR Gln223Arg gene polymorphism with obesity, leptin, insulin resistance, and metabolic abnormalities.