Relationship between CCR5+FoxP3+ Treg cells and forced expiratory volume in 1 s, peak expiratory flow in patients with severe asthma.

INTRODUCTION: Severe asthma is a special clinical problem. CD4+CD25highCD127lowFoxp3+ Tregs play a role in maintaining appropriate immunological response. It is a known fact that Treg cells with CCR5 expression represent strong suppressive activity. It has been shown that a low number or altered function of FoxP3+ Tregs is associated with the inflammatory process and airway obstruction in asthma. AIM: To evaluate whether CCR5 Tregs expression and surface density on FoxP3+ Treg cells depend on the severity of asthma. MATERIAL AND METHODS: The study included 50 patients with asthma (25 with severe and 25 with mild-to-moderate asthma). The control group comprised 25 healthy volunteers. The phenotype of CD4+CD25highCD127lowFoxp3+CCR5+ cells was evaluated by multicolour flow cytometry. The degree of airflow obstruction was assessed by spirometry as forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF). RESULTS: The absolute count of FoxP3+ Treg cells in patients with severe asthma was significantly decreased in comparison with the control group. MFI (median fluorescence intensity) of CCR5 expression on FoxP3+ Treg cells was significantly decreased in severe asthma compared to the mild-to-moderate asthma and control groups. CCR5 expression on FoxP3+ Treg cells as MFI positively correlated with lung function parameters FEV1% and PEF% in patients with severe asthma. CONCLUSIONS: High CCR5 Tregs expression as MFI is associated with improved in lung function parameters: FEV1% and PEF% in patients with severe asthma. The measurement of CCR5 expression on the surface of peripheral blood FoxP3+ Treg cells as MFI could be an additional tool to estimate the severity of asthma.

CCR6 blockade on regulatory T cells ameliorates experimental model of multiple sclerosis.

Regulatory T cells (Tregs) play a significant role in limiting damage of tissue affected by autoimmune process, which has been demonstrated in various experimental models for multiple sclerosis (MS) (mostly experimental autoimmune encephalomyelitis - EAE), rheumatoid arthritis, and type 1 diabetes. In this study, we demonstrated that Tregs increasingly migrate to central nervous system (CNS) during subsequent phases of EAE (preclinical, initial attack, and remission). In contrast, in peripheral tissues (blood, lymph nodes, and spleen), a significant accumulation of Tregs is mostly present during EAE remission. Moreover, an increased expression of CCR6 on Tregs in the CNS, blood, lymph nodes, and spleen in all phases of EAE was observed. The highest expression of CCR6 on Tregs from the CNS, lymph nodes, and spleen was noted during the initial attack of EAE, whereas in the blood, the peak expression of CCR6 was detected during the preclinical phase. The presence of Tregs in the CNS during EAE was confirmed by immunohistochemistry. To analyze additional functional significance of CCR6 expression on Tregs for EAE pathology, we modulated the clinical course of this MS model using Tregs with blocked CCR6. EAE mice, which received CCR6-deficient Tregs showed significant amelioration of disease severity. This observation suggests that CCR6 on Tregs may be a potential target for future therapeutic interventions in MS.

The relationship between peripheral blood mononuclear cells telomere length and diet - unexpected effect of red meat.

BACKGROUND: Repeated nucleotide sequences combined with proteins called telomeres cover chromosome ends and dictate cells lifespan. Many factors can modify telomere length, among them are: nutrition and smoking habits, physical activities and socioeconomic status measured by education level. The aim of the study was to determine the influence of above mentioned factors on peripheral blood mononuclear cells telomere length. METHODS: Study included 28 subjects (seven male and 21 female, age 18-65 years.), smokers and non-smokers without any serious health problems in past and present. Following a basic medical examination, patients completed the food frequency questionnaire with 17 foods and beverages most common groups and gave blood for testing. PBMC telomere length were measured with qualitative real-time Polymerase Chain Reaction (rtPCR) method and expressed as a T/S ratio. RESULTS: Among nine food types (cereal, fruits, vegetables, diary, red meat, poultry, fish, sweets and salty snacks) and eight beverages (juices, coffee, tea, mineral water, alcoholic- and sweetened carbonated beverages) only intake of red meat was related to T/S ratio. Individuals with increased consumption of red meat have had higher T/S ratio and the strongest significant differences were observed between consumer groups: "never" and "1-2 daily" (p = 0.02). Smoking habits, physical activity, LDL and HDL concentrations, and education level were not related to telomere length, directly or as a covariates. CONCLUSIONS: Unexpected correlation of telomere length with the frequency of consumption of red meat indicates the need for further in-depth research and may undermine some accepted concepts of adverse effects of this diet on the health status and life longevity.

The impact of multiple sclerosis relapse treatment on migration of effector T cells--Preliminary study.

UNLABELLED: Migration of inflammatory cells from the blood to the central nervous system (CNS) is crucial for development of multiple sclerosis (MS). Inhibition of this process would allow to control disease activity. The first step confirming this approach would be the analysis of the impact of effective MS relapse therapy on migration of effector T cells. The aim of the study was to analyze the influence of methylprednisolone (MP) on the migratory activity of effector CD4+ T cells from MS patients. Moreover, to study the potential mechanism of this process we studied expression of chemokine receptors on migrating cells. MATERIAL AND METHODS: Peripheral blood samples were obtained from relapsing-remitting MS (RR-MS) patients during relapse (n=23) and from control group (n=23). After isolation CD4+ T cells were incubated with various concentrations of MP. Then they were stimulated in chemotaxis assay with chemokines CCL3 or CXCL10 or were used to CCR1 and CXCR3 expression analysis. RESULTS: CXCL10- and CCL3-stimulated migration of CD4+ T cells was significantly increased in MS. MP was able to reduce in vitro migration of effector T cells induced by CXCL10, but not by CCL3. Inhibition by MP was dose-dependent. Expression of analyzed chemokine receptors was unaltered after MP incubation. CONCLUSIONS: MP reduced CD4+ T cells migration induced by CXCL10 without affecting CXCR3 expression. These observations demonstrate one of the potential mechanisms of MP action in MS, distinct from inducing cell apoptosis, and suggests the new targets for development of more effective MS treatments.

Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.

Interleukin 18 as an early marker or prognostic factor in acute pancreatitis.

INTRODUCTION: Acute pancreatits (AP) still reqiures better diagnostic and therapeutic options to be introduced in order to decrease its morbidity and mortality. It appears that the assessment of serum levels of interleukin 18 (IL-18) and its correlation with C-reactive protein (CRP) may provide adequate prognostic value. AIM: To measure serum concentrations of IL-18 and inflammation markers such as CRP in patients with AP during subsequent hospital stay days and to assess the role of IL-18 as an early AP marker and prognostic factor. MATERIAL AND METHODS: Thirty-two patients aged 47 ±16.7 years were included into the study (17 males and 15 females), in whom AP was diagnosed based on ultrasound and computer aided tomography imaging and amylase. Serum amylase, CRP, and IL-18 levels were measured on the 1(st), 2(nd), 3(rd), and 5(th) days of hospital stay. All patients were scored "B" according to Balthazar and mild AP based on Ranson criteria. The control group consisted of 30 healthy volunteers aged 50.7 ±12.4 years (15 males and 15 females). RESULTS: The average IL-18 serum level in the control group was 86.91 ±4.94 pg/ml. Mean IL-18 study group levels were 128.4 ±7.6 pg/ml on the 1(st), 112.0 ±4.4 pg/ml on the 3(rd), and 122.8 ±6.8 pg/ml on the 5(th) day of AP, and were significantly higher than those in the control group, accordingly: p < 0.001, p < 0.005, p < 0.001. A positive correlation between IL-18 and CRP serum concentrations was observed. A slight increase in correlation was observed as the days went by. CONCLUSIONS: We concluded that the serum IL-18 level increases in the initial phase of AP, and it may be used as an inflammatory reaction marker in patients with AP, and it is correlated with CRP, which may indicate its prognostic role in AP.

The patents on glucocorticosteroids and selected new therapies for the management of asthma in children: update.

Despite the continuous increase in the prevalence of asthma in many developing countries, there have been major advances in understanding and managing this disease. The remarkable role of inflammation in asthma is well known. Current asthma guidelines recommend the use of anti-inflammatory drugs and immunotherapy for long-term management of asthma. The management of asthma in children is a challenge because of their inability to express warning signs and seek medical attention in a timely manner. Unlike adults, asthmatic children must rely on their parents or caregivers for the administration of asthma medications. The inability to carry and self-administer asthma drugs may increase the risk of non-compliance. Glucocorticosteroids, the most important drugs for patients with asthma, are associated with an increased level of side effects and compliance issues mostly in children. In an attempt to solve that dilemma, emphasis is being placed on the modification of current management tactics and the introduction of other drugs. This review presents more recent patents for childhood asthma therapies for the management of asthma in children.

Serum adiponectin, resistin, leptin concentration and central adiposity parameters in Barrett's esophagus patients with and without intestinal metaplasia in comparison to healthy controls and patients with GERD.

BACKGROUND/AIMS: Central obesity is a risk factor for GERD, Barrett's esophagus and esophageal adeno-carcinoma. Recent studies have suggested that adipocytokines are the possible link between adiposity and Barrett's carcinogenesis. To determine the adiponectin, resistin and leptin concentration as well as the central adiposity parameters in BE patients with and without intestinal metaplasia (IM) in comparison to GERD and healthy controls. METHODOLOGY: Total of 77 patients (30 patients with GERD, 26 BE with IM and 21 BE without IM) and 30 healthy controls were investigated for the central obesity parameters. Serum levels of adipocytokines were measured with ELISA. RESULTS: The serum concentration of adiponectin was significantly lower in BE compared to those in GERD and to controls (p<0.001). Levels of leptin was slightly higher in BE than in GERD and controls (NS). Level of resistin was significantly higher in GERD compared to both control and BE patients (p<0.001). Waist circumference, WHR and WTR were significantly higher in BE patients compared to GERD (p<0.001) and to control group (p<0.001). CONCLUSIONS: Features of central obesity rather than BMI are associated with BE development. Adipokines may be important at the early step of BE development, before the IM occurrence.

[The use of multi-color flow cytometry for identification of functional markers of nTregs in patients with severe asthma]. / Wykorzystanie wielokolorowej cytometrii przeplywowej do identyfikacji markerów czynnosciowych limfocytów nTreg u chorych na ciezka astme oskrzelowa.

INTRODUCTION: At present, severe asthma is a particular clinical problem. An important role is attributed to dysfunction of nTreg subpopulations of lymphocytes in the pathogenesis of asthma. Therefore, the purpose of this study was to identify markers of nTreg cell function in patients with severe and mild to moderate asthma. MATERIAL AND METHODS: The study included sixty patients with asthma (30 with severe and 30 with mild to moderate asthma). The control group comprised 30 healthy volunteers. The diagnosis of asthma was confirmed accordance with generally accepted recommendations (GINA 2008). nTreg immunophenotype CD4/CD25/CD127/FoxP3/GITR/CD152/CCR5/ /CCR7 was evaluated by multicolor flow cytometry. RESULTS: We showed a significant reduction in the percentage of nTreg (76%) cells and the expression of CD152 (46.2%) in patients with severe asthma compared with mild-moderate asthma (85.5% and 86.7%; p 〈 0.05). It was observed that the transcription factor FoxP3 expression in nTreg cells positively correlated with FEV1 in patients with severe asthma (r = 0.53; p 〈 0.05). It was also found that the ratio nTregCCR5∗/TeffCCR5∗ was significantly reduced in patients with severe asthma (0.91) compared with mild-moderate (1.58) asthma and control groups (1.55; p 〈 0.001). CONCLUSIONS: There are phenotypic differences in nTreg lymphocytes between patients with severe and mild-moderate asthma. This fact may confirm nTreg cell dysfunction and indicate that the potential markers (FoxP3, CD152, CCR5), can be used to monitor the effectiveness of treatment of bronchial asthma, especially severe disease.

Evaluation of the relationship between leptin, resistin, adiponectin and natural regulatory T cells in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Data suggest that adipocytokines and natural regulatory T (nTreg) cells play a pivotal role in the immunopathogenesis of multiple sclerosis and the associated inflammation. The purpose of this study was to evaluate selected adipocytokines and nTreg cells and to assess their relationship with relapsing-remitting multiple sclerosis (RRMS). MATERIAL AND METHODS: The study was conducted among 25 patients with RRMS and 25 healthy individuals. Blood samples were collected within two weeks after the beginning of acute relapse of RRMS. The body mass index (BMI) of each patient was calculated. Serum adipocytokine concentrations were determined by ELISA and nTreg cells were evaluated using multicolour flow cytometry. RESULTS: Patients and controls had similar BMI, regardless of gender. Significantly higher leptin and resistin levels and significantly lower adiponectin levels were found in patients with RRMS in comparison to the control group (p < 0.0001). The percentage of nTreg cells (p < 0.01) and the mean fluorescence channel (MFC) of FoxP3 were significantly reduced in patients with RRMS (p < 0.001). There was an inverse correlation be-tween leptin concentration and MFC of the transcription factor Foxp3 nTreg in patients with RRMS (r = -0.7, p < 0.05). CONCLUSIONS: Proinflammatory adipocytokine profile and decreased percentage of nTreg cells suggest their implication in the inflammatory response in RRMS regardless of corticosteroid therapy. The correlation between leptin and the MFC of the transcription factor Foxp3 in nTreg cells in patients with RRMS suggests its inhibitory effect on FoxP3 expression.

The patents on glucocorticosteroids and selected new therapies for the management of asthma in children.

Despite the continuous increase in the prevalence of asthma in the most underdeveloped parts of the world, nowadays, we can generally speak of a better understanding and management of this disease. The remarkable role played by the inflammatory process in asthmatic patients is well known. The aim of most asthma guidelines is to suppress inflammatory process with a combination of anti-inflammatory drugs and immunotherapy. The management of asthma in children is a challenge because of their inability to express warning signs and seek medical attention in a timely manner. Unlike adults, asthmatic children must rely on their parents or caregivers for the administration of asthma medications. This inability to carry and self-administer asthma drugs may increase the risk of non-compliance. Glucocorticosteroids, the most important drugs for patients with asthma, are associated with an increased level of side effects and compliance issues mostly in children. In an attempt to solve that dilemma, emphasis is being placed on the modification of current management tactics and the introduction of other drugs. This review presents more recent patent therapies for the management of asthma in children.

The application of Montreal classification in different clinical and serological IBD subtypes.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) represents the heterogeneous group of disorders with a wide variety of clinical manifestations. The Montreal classification has been developed recently and its accuracy in categorizing of IBD phenotypes needs to be investigated. The aim of the study was to assess the usefulness of the Montreal classification compared to CAI and CDAI in various disease activity, serological and clinical manifestations of IBD. METHODOLOGY: The study was performed in 125 IBD patients: 71 patients with ulcerative colitis, 31 with Crohn's disease and 23 with IBD unclassified (indeterminate colitis). Disease activity and clinical course were assessed using Montreal classification, Clinical Activity Index and Crohn's Disease Activity Index. pANCA and ASCA were measured with ELISA, using widely used, commercial antibody panel (Cogent Diagnostics and Genesis Diagnostics and MedTek kits). RESULTS: No significant correlation has been found between pANCA/ASCA presence and disease activity using CAI and CDAI. ASCA and pANCA-/ASCA+ antibodies pattern had been detected more often in patients with Crohn's disease after surgery, with localization in small or small and large intestine, without perianal lesions and with early disease onset. CONCLUSIONS: Correlations between serotype and certain clinical phenotype are present, which could potentially be of value in the classification of patients particular treatment regimen. We have noticed that clinical course assessment using Montreal classification shows precisely real CD patients state.

Circulating levels of visfatin, resistin and pro-inflammatory cytokine interleukin-8 in acute pancreatitis.

BACKGROUND: Resistin and visfatin, hormones produced by adipose tissue, have pro-inflammatory potential; however, their role in acute pancreatitis (AP) has been investigated only rarely. METHODS: The study group comprised 32 patients with alcoholic AP and 30 controls. In all cases AP was classified as C according to Balthazar's CT score and as severe according to Ranson's criteria. The serum level of visfatin, resistin, and interleukin(IL)-8 immunoassays were measured by ELISA on admission and on the third and fifth day of hospitalization. RESULTS: On the admission day serum resistin and IL-8 concentrations in AP patients were significantly higher than in controls and they further increased on the third and fifth day of hospitalization. On the admission day serum visfatin levels in AP patients were significantly higher than in controls and further increased on the third day of hospitalization. On the fifth day the levels decreased; however, they were still higher than on admission. The correlation between visfatin and resistin as well as between C-reactive protein and visfatin, resistin and IL-8 levels has been found. CONCLUSION: In the course of AP, visfatin and resistin levels increase in parallel with C-reactive protein. We speculate that those parameters may provide an additional tool for the prognosis and monitoring of AP. and IAP.

Usefulness of assessing circulating levels of resistin, ghrelin, and IL-18 in alcoholic acute pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is a severe inflammatory disease with high mortality and morbidity rates. We have previously demonstrated that resistin may represent an early marker of inflammation in AP. It was also revealed that ghrelin may have anti-inflammatory potential. However, the role of adipohormones in AP-resistin and ghrelin as well as the proinflammatory cytokine interleukin (IL)-18-has not yet been fully elucidated. METHODS: The study group comprised 32 patients with alcoholic AP and 30 controls matched for age, sex, and body mass index (BMI). In all cases AP was classified as grade C according to Balthazar's computed tomography (CT) score and as severe (3 points) according to Ranson's criteria. Serum levels of resistin, ghrelin, and IL-18 were measured on first, third, and fifth day of hospitalization by enzyme-linked immunosorbent assay (ELISA). RESULTS: On first day of hospitalization the mean serum resistin concentration in AP patients was significantly higher than in controls (P < 0.05) and further increased on third and fifth day of hospitalization (17.4 ± 4.23 ng/ml and 25.8 ± 8.14 ng/ml, respectively). On first day of hospitalization the mean serum IL-18 concentration in AP patients was significantly higher than in controls (P < 0.05), on third day its level further increased, and on fifth day it decreased to a level similar to that observed on admission. The serum ghrelin concentrations on first, third, and fifth day of hospitalization were comparable, and significantly higher than in controls (P < 0.01). Significant correlation between C-reactive protein (CRP) and resistin levels (r = 0.43; P < 0.05) and between CRP and IL-18 (r = 0.58; P <0.05) on day of admission was found. CONCLUSIONS: Serum concentration of IL-18 and resistin may contribute to inflammatory response and may be useful as an early marker of inflammation in AP. We also suspect that ghrelin affects the course of AP and plays an important role in inflammatory response.

Serum leptin, adiponectin, and resistin concentration in colorectal adenoma and carcinoma (CC) patients.

INTRODUCTION: Leptin, adiponectin, and resistin are the proteins secreted by adipocytes, which affects the metabolism. While the role of leptin in colon carcinogenesis is documented, the effect of adiponectin and resistin remains unclear. It has been indicated that while leptin may potentiate the cancer cells growth, adiponectin and resistin may act oppositely. AIM: The aim of this study is to determine the concentration of leptin, adiponectin, and resistin in patients with adenomatous polyps and colorectal cancer. METHODS: The serum concentration investigated adipohormones had been measured with ELISA in 37 patients with colorectal adenomas, 36 with colorectal cancer (CC) and in 25 controls with no colorectal pathology. Endoscopically removed polyps and CC biopsies had been evaluated with histopathology. Mean BMI value was calculated for all patients. RESULTS: Among 37 adenomas, 25 revealed high-grade dysplasia (HGD) and 12 low-grade dysplasia (LGD). All cases of CC were adenocarcinomas. No difference in the level of investigated adipohormones in serum between patients with HGD and LGD polyps was observed. The serum concentration of leptin and adiponectin in CC patients was lower than in patients with adenomas (p < 0.05; p < 0.05, respectively) as well as in controls (p < 0.01; p < 0.05, respectively). The concentration of resistin in CC was not significantly different in the adenoma group (p > 0.05) but higher than in controls (p < 0.05). There was a correlation between adiponectin and leptin serum concentration (r = 0.61). CONCLUSION: We conclude that serum concentration of adiponectin and resistin may play an important role in colon carcinogenesis. We also assume that leptin may possibly have the prognostic value useful in clinical practice and its concentration is independent of BMI value.

[Serum concentration of insulin, C-peptide and insulin-like growth factor I in patients with colon adenomas and colorectal cancer]. / Stezenie insuliny, C-peptydu i insulinopodobnego czynnika wzrostu I w surowicy chorych z polipami i rakiem jelita grubego.

UNLABELLED: Colon carcinogenesis is a multi-steps process in which many growth factors are involved. In some studies the increased risk of colon cancer development was observed in patients with diabetes mellitus type 2 with accompanying hyperinsulinemia. It is also known that insulin-like growth factor I (IGF-I) plays an important role in proliferation, growth, differentiation and inhibiting apoptosis of both epithelial and carcinoma cells. The aim of the study was to evaluate the serum concentration of insulin, C-peptide and IGF-I in patients with colon adenomas and colorectal cancer. MATERIALS AND METHODS: In 17 patients with colon cancer, 32 patients with colon adenomas and in 12 healthy persons the serum concentration of insulin, C-peptide and IGF-I was determined using ELISA kits. RESULTS: In patients with colon cancer significantly higher serum IGF-I concentration comparing to the control group was observed (85.66 ng/ml vs. 60.96 ng/ml; p < 0.05). Higher IGF-I concentration was also observed in patients with distal tumors comparing to the proximal localisation (95.40 ng/ml vs. 64,65 ng/ml, p < 0.05) and in more differentiated tumors (84.36 ng/ml vs. 75.24 ng/ml). Similarly, higher C-peptide concentrations were observed in distal tumors (635.64 pmol/ I vs. 578.69 pmol/l) and in well-differentiated carcinoma (671.32 pmol/ I vs. 575.66 pmol/l). In patients with colon adenomatous polyps we also observed higher serum IGF-I concentrations I comparing to the control group (82.1 ng/ml vs. 60.96 ng/ml), in high dysplasia adenomas (84.12 ng/ml vs. 79.67 ng/ml) and in smaller adenomas to 1 cm diameter (97.98 ng/ml vs. 73.28 ng/ml), but the differences were not significant. We also observed higher concentration of C-peptide in patients with low grade dysplasia adenomas (665.24 pmol/l vs. 498.13 pmol/l) and with small polyps (611.51 pmol/l vs. 514.89 pmol/l). There were no differences in serum concentration of IGF-I and C-peptide between patients with tubular and villous adenomas. There was no statistical difference observed in insulin serum concentration in all groups of patients. CONCLUSIONS: IGF-I is probably involved particularly in the early stage of colon carcinogenesis.

[Resistin-- a new laboratory marker useful in diagnosis of acute pancreatitis?]. / Rezystyna--nowy marker laboratoryjny przydatny w rozpoznaniu ostrego zapalenia trzustki?

UNLABELLED: Acute pancreatitis (AP) is the severe disease with high mortality and morbidity which pathomechanism is still not clearly elucidated yet. Serum pro-inflammatory cytokines like Interleukin-18, TNF alpha, and C-reactive protein (CRP) are elevated in patients with AP, particularly of severe clinical course. Adipocytes hyperplasia is a trigger factor that initiates chronic inflammatory state which release adipocytokines, like TNF alpha or leptin or resistin. The aim of the present study was to assesses the serum resistin concentrations in AP patients and evaluate the correlation between resistin and the well known inflammation marker--CRP. MATERIAL AND METHODS: The study group comprised 30 patients with acute pancreatitis class B according to Balthazar scale, aged 35-82, in which during first 24h of hospitalization serum resistin and CRP has been assessed. Control group consisted of 30 healthy volunteers, aged 33-76. RESULTS: The mean serum resistin concentration was significantly higher in AP patients than in controls (8,38 +/- 4.87 ng/ml vs. 3.58 +/- 1.51 ng/ml) (fig. 1). The positive correlation between serum resistin and CRP concentrations has been observed (r = 0.57, p < 0.05) (fig. 2). CONCLUSIONS: The results of our study suggest, that the serum concentration of resistin may represent the useful additionary marker of inflammatory response in AP

[The influence of erythropoietin (Epo) on intercellular adhesion molecule-1 (ICAM-1, CD54) and platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) expression on human umbilical vein endothelial cells (HUVEC) induced by tumor necrosis factor-alpha (TNF-alpha)]. / Wplyw erytropoetyny (Epo) na indukowana czynnikiem martwicy nowotworów-alpa (tnf-alpha) ekspresje czasteczek adhezji miedzykomórkowej-1 (ICAM-1, CD54) i czasteczek adhezji komórkowej plytek i sródblonka-1 (PECAM-1, CD31) na powierzchni komórek sródblonka ludzkiej zyly pepowinowej (HUVEC).

UNLABELLED: The latest research proved that erythropoietin (Epo), a sensitive to hypoxia physiological erythropoiesis regulator, used successfully to treat anemia, displays cytoprotective, angiogenic, anti-inflammatory, anti-oxidative and anti-apoptotic properties. The aim of the study was to examine the influence of Epo on intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM--1) expression on human umbilical vein endothelial cells (HUVEC) induced by tumor necrosis factor-a (TNF-alpha). MATERIAL AND METHODS: Human umbilical vein endothelial cells were cultured in a standard medium (M 199). The experiment was performed five times on the forth passage of HUVEC culture. For stimulation TNF-alpha was used in concentrations: 10, 20, 40 ng/ml (6 hours) and Epo in concentrations: 10, 20, 40 IU/ml (24 hours). The expression level of ICAM-1 and PECAM-1 on HUVEC were quantified by flow cytometry. RESULTS: The Incubation of HUVEC with TNF-a significantly increased the ICAM-1 and PECAM-I expression. The cultures pretreated with Epo reduced ICAM-1 and PECAM-I expression induced by TNF-a from 70.0 +/- 3.94% to 59.3 +/- 0.60% and from 83.4 +/- 2.27% to 57.7 +/- 0.66% respectively for ICAM-1 and PECAM-1. CONCLUSIONS: Erythropoietin statistically significantly decreases ICAM-1 and PECAM-1 expression on HUVEC stimulated by TNF-alpha.

Expression of multidrug resistance P-glycoprotein on lymphocytes from nephrotic children treated with cyclosporine A and ACE-inhibitor.

The aim of this work was to determine the expression of P-glycoprotein (P-gp) on peripheral lymphocytes (CD3) in children with steroid-dependent nephrotic syndrome (SDNS) during cyclosporine A (CyA) and ACE-inhibitor (ACE-I) treatment. The study group (I) consisted of 20 children with SDNS aged 5-18 years, with a subsequent proteinuria relapse at the time of prednisone dose reduction. All nephrotic syndrome (NS) children were examined three times: A--at proteinuria relapse, before CyA treatment; B--after 3 months; C--after 12 months of CyA administration. The control group (II) consisted of 20 healthy children. CD3/P-gp was measured using a flow cytometry assay. The serum CyA level was assessed by means of the immunofluorescence method. The expression of CD3/P-gp in NS relapse, prior to CyA+ACE-I administration, was much higher (median 9.15%, range 1.50-13.50%) when compared to healthy controls (median 1.20%, range 0.30-5.70%). The absolute number of CD3/P-gp in this examination was almost five times higher when compared to healthy controls (p<0.01). After 3 months of CyA+ACE-I therapy, the expression of CD3/P-gp decreased dramatically and was similar to the controls. Similar results were obtained after 12 months of treatment. A strong negative correlation was found between CD3/P-gp and serum CyA concentration in both examinations (r=-0.624, p<0.01; r=-0.464, p<0.01). We conclude that the results of our studies indicate that CyA+ACE-I in SDNS inhibits the expression of P-gp. CyA is an alternative therapy that may lead to the optimization of glucocorticoid (GC) doses, thus, reducing the risk that is associated with the treatment.

Alteration of peripheral blood lymphocyte subsets in acute pancreatitis.

AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP). METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5, 10 and 30 by means of flow cytometry. RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of T- over B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28, CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5, IL-10, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells. CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.