Ferah Budak

IL‐10 and TGF‐β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy

The regulation of normal and allergic immune responses to airborne allergens in the mucosa is still poorly understood, and the mechanism of specific immunotherapy (SIT) in normalizing the allergic response to such allergens is currently not clear. Accordingly, we have investigated the immunoregulatory mechanism of both normal and allergic responses to the major house‐dust mite (HDM) and birch pollen allergens — Dermatophagoides pteroynyssinus (Der p)1 and Bet v 1, respectively — as well as the immunologic basis of SIT to HDM in rhinitis and asthma patients. In normal immunity to HDM and birch pollen, an allergen‐specific peripheral T cell suppression to Der p 1 and Bet v 1 was observed. The deviated immune response was characterized by suppressed proliferative T celland Th1 (IFN‐γ) and Th2 (IL‐5, IL‐13) cytokine responses, and increased IL‐10 and TGF‐β secretion by allergen‐specific T cells. Neutralization of cytokine activity showed that T cell suppression was induced by IL‐10 and TGF‐β during SIT and in normal immunity to the mucosal allergens. In addition, SIT induced an antigen‐specific suppressive activity in CD4+ CD25+ T cells of allergic individuals. Together, these results demonstrate a deviation towards a regulatory/suppressor T cell response during SIT and in normal immunity as a key event for the healthy immune response to mucosal antigens.

Urinary IL-18: a marker of contrast-induced nephropathy following percutaneous coronary intervention?

OBJECTIVES Contrast-induced nephropathy (CIN) is a complication that is underestimated in clinical practice after cardiac catheterization. Recently, the value of interleukin (IL)-18 as a novel biomarker for the detection of acute renal failure has been highlighted. In the present study, we sought to investigate whether urine IL-18 may be an early diagnostic marker of CIN. DESIGN AND METHODS We performed a nested case-control study using a hospital based cohort of all patients (n=157) admitted for elective PCI for stable angina to the Uludag University School of Medicine between February 2007 and June 2007. We identified 15 patients (9.5%) with CIN. Controls were matched with cases at an attempted 2.5:1 ratio by age and gender. Urinary IL-18 values were measured before as well as 24 and 72 h after the PCI. RESULTS No statistically significant differences in urine IL-18 were detected between cases (n=15) and controls (n=36) or between the patient samples obtained before PCI and after the invasive procedure in both study groups. CONCLUSIONS These findings argue against the hypothesis that urine IL-18 may be clinically useful as a biomarker of CIN after radiological procedures requiring intravascular administration of iodinated contrast media. Further studies with larger sample sizes are needed to validate our findings.

Effect of Saccharomyces boulardii in Children with Acute Gastroenteritis and Its Relationship to the Immune Response

We evaluated the effect of Saccharomyces boulardii administration in otherwise healthy children aged between 6 months and 10 years who were admitted for acute diarrhoea (15 males, 12 females). The patients were randomized into two groups: group 1 (n = 16) received 250 mg S. boulardii dissolved in 5 ml of water orally twice daily for 7 days and group 2 (n = 11) received placebo. Clinical and laboratory assessments were performed on admission and on day 7 of follow-up. Both groups experienced reduced daily stool frequency, the decrease being significantly greater in group 1 on days 3 and 4 compared with group 2. Group 1 demonstrated significant increases in serum immunoglobulin A and decreases in C-reactive protein levels on day 7. The percentage of CD8 lymphocytes on day 7 was significantly higher in group 1 than group 2. This study confirmed the efficacy of S. boulardii in paediatric acute gastroenteritis and the findings suggest that S. boulardii treatment enhances the immune response.

Effect of rosiglitazone, metformin and medical nutrition treatment on arterial stiffness, serum MMP-9 and MCP-1 levels in drug naive type 2 diabetic patients.

The aim of the study was to evaluate the long-term effect of rosiglitazone and metformin monotherapy with medical nutrition treatment (MNT) and of MNT alone on arterial stiffness, serum monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9 in drug naive patients with type 2 diabetes mellitus. Fifty type 2 diabetic patients were randomized to receive rosiglitazone 4 mg/day (n=19) or metformin 850 mg/day (n=16) with MNT or MNT alone (n=15), for 52 weeks. Arterial stiffness was assessed by using large and small artery elasticity index (SAEI and LAEI, respectively). SAEI, LAEI, serum MCP-1 and MMP-9 levels were measured at baseline and following 52 weeks of treatment. SAEI was improved only in the rosiglitazone group, and the difference was still statistically significant when the three groups were compared (p=0.024). There were no differences in LAEI in inter- and intragroup comparisons at the end of the study. Serum MMP-9 levels were decreased in the metformin (-13.5+/-34.8%, p=0.02) and rosiglitazone (-27.2+/-51.0%, p=0.023) groups compared with baseline values, whereas no significant change was seen in serum MCP-1 levels. These results suggest that rosiglitazone monotherapy has favorable effects on arterial stiffness compared with metformin monotherapy independent of glycemic control.

Increased Pleural Soluble Fas Ligand (sFasL) Levels in Tuberculosis Pleurisy and Its Relation with T-helper Type 1 Cytokines

Tuberculosis (TB) pleurisy is accepted to be the best model for evaluating the local protective cellular immune response to Mycobacterium tuberculosis (MTB) since it can be spontaneously self-cured. Therefore, we aimed to evaluate the involvement of cytokines and the soluble apoptosis-modulating factors sFas and sFasL in local protective cellular immunity to MTB. Pleural fluid samples were collected from 35 patients with TB pleurisy, 39 patients with malignant pleurisy, and 14 patients with non-TB nonmalignant (n-TB n-M) pleurisy and were evaluated for the levels of several cytokines, soluble Fas (sFas), and sFas ligand (sFasL) by using ELISA. The levels of IFN-γ, IL-12p40, IL-18, IL-8, and sFasL in TB pleurisy were significantly higher in comparison to those in the malignant pleurisy and n-TB n-M pleurisy groups. In addition, pleural sFasL levels were increased and positively correlated with IFN-γ and IL-18 levels in TB patients. In conclusion, this study demonstrates that Th1-type-specific cellular immunity is responsible for protective immunity in TB and suggests that Fas-mediated apoptosis may be at least a part of protective immunity to tuberculosis and could be regulated by type 1 T-cell response. IFN-γ and sFasL levels can be used as diagnostic markers for differing TB pleurisy from other pleurisies.

Lymphocyte subsets and cytokines in ascitic fluid of decompensated cirrhotic patients with and without spontaneous ascites infection

Background and Aim:  Spontaneous ascites infection is a frequently encountered and important complication of decompensated liver cirrhosis. The immune system plays an important role in the development or eradication of this infection. A number of compositional and functional alterations in immune system cells have been demonstrated in cirrhotic patients; however, there is a lack of knowledge about this issue in ascitic infections. The aim of the present study was to evaluate lymphocyte subsets and levels of some ascitic and lymphocytic intracytoplasmic cytokines in decompensated cirrhotic patients with or without spontaneous ascites infection.

Comparison of three different treatment modalities in the management of cancer cachexia

AIMS AND BACKGROUND The optimal treatment of cancer cachexia remains unknown. In this study, we compared the efficacy of three different treatment modalities in the management of cancer cachexia. METHODS Sixty-two assessable cachectic cancer patients were randomized to one of the following three arms: 1) megesterol acetate (MA) plus meloxicam (n = 23); 2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement (n = 21); or 3) meloxicam plus oral EPA-enriched nutritional supplement (n = 18). Treatment duration was 3 months. RESULTS The treatment arms were well balanced at baseline. The primary efficacy (body weight and lean body mass) and secondary efficacy (body mass index, quality of life, and serum levels of IL-6 and TNF-α) parameters improved after treatment in all three arms. There were no statistically significant differences between treatment groups in the mean percentage changes in all efficacy parameters from baseline to end of study. CONCLUSIONS MA plus meloxicam or EPA supplement plus meloxicam may be effective treatment options in the management of cancer cachexia. The combined use of these agents does not provide further advantages.

Effect of levothyroxine treatment on clinical symptoms and serum cytokine levels in euthyroid patients with chronic idiopathic urticaria and thyroid autoimmunity

Background.  Screening for thyroid autoimmunity in patients with chronic idiopathic urticaria (CIU) is generally recommended. However, there are not yet sufficient data as to whether levothyroxine treatment is beneficial for the clinical symptoms of CIU in patients with thyroid autoimmunity.

MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

Although our knowledge about Brucella virulence factors and the host response increase rapidly, the mechanisms of immune evasion by the pathogen and causes of chronic disease are still unknown. Here, we aimed to investigate the immunological factors which belong to CD8+ T cells and their roles in the transition of brucellosis from acute to chronic infection. Using miRNA microarray, more than 2000 miRNAs were screened in CD8+ T cells of patients with acute or chronic brucellosis and healthy controls that were sorted from peripheral blood with flow cytometry and validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Expression of two miRNAs were determined to display a significant fold change in chronic group when compared with acute or control groups. Both miRNAs (miR-126-5p and miR-4753-3p) were decreased (p <0.05 or fold change > 2). These miRNAs have the potential to be the regulators of CD8+ T cell-related marker genes for chronic brucellosis infections. The differentially expressed miRNAs and their predicted target genes are involved in MAPK signaling pathway, cytokine-cytokine receptor interactions, endocytosis, regulation of actin cytoskeleton, and focal adhesion indicating their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human CD8+ T cells to clarify the mechanism of inveteracy in brucellosis.

Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis

Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10–30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p < 0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.