Effects of allergen-specific immunotherapy on functions of helper and regulatory T cells in patients with seasonal allergic rhinitis.

BACKGROUND: Seasonal allergic rhinitis (SAR) is characterized by a helper T (Th)2 cell-mediated immune response at the target site. There is a relative Th1 and/or regulatory T (Treg) cell insufficiency in patients with SAR. It has been demonstrated that there is a change in the balance between these cells after allergen-specific immunotherapy (SIT), which is a curative treatment modality for this disease. However, there are few studies that evaluate the number and function of these cells in the inflammatory area after SIT treatment. OBJECTIVE: We aimed to investigate the distribution of Th1, Th2 and Treg cells in nasal biopsies and lavage fluid (NLF) specimens from patients with SAR, before and after SIT. METHODS: Twenty-four, symptomatic SAR patients sensitized to Olea europeae, were enrolled in the study prior to treatment. Fifteen, non-allergic subjects with nasal septum deviation, who needed surgical treatment, served as the control group. NLF and inferior turbinate biopsies were obtained from both groups during the pollen season. Conventional, subcutaneous SIT with Olea europeae extract was initiated in patients with SAR. One year after the first biopsy, biopsies and NLF specimens were again obtained for reevaluation. All biopsies were evaluated for Th1, Th2 and Treg cell counts by means of their transcription factors (T-bet, GATA-3 and FoxP3) using an immunohistochemical analysis method. Additionally, all NLF specimens were evaluated for the functions of these cells, by means of their specific cytokines, using an ELISA method. RESULTS: When the basal status of those patients with SAR was evaluated based on transcription factors, prior to treatment, Th1 and Treg cells were found to be fewer than in non-allergic controls (p=0.001 for both T-bet and FoxP3). It was demonstrated that numbers of GATA-3-carrying cells, which are a marker for Th2, were not significantly different between the groups (p=0.276), but evaluation of the Th1/Th2 ratio revealed a relative Th2 dominance in patients with SAR prior to treatment. When evaluated on the basis of cytokine levels, it was observed that Th1-originated IFN-γ was lower in patients with SAR compared to the control group, both before and after treatment (p=0.012 for both comparisons), Th2-originated IL-4 levels were not significantly different between the groups either before or after treatment (p=0.649, p=0.855; respectively). Th2- and Treg cell-originated IL-10 levels were higher in patients with SAR before treatment (p=0.033), but this difference was not statistically signifant following treatment compared with controls (p=0.174). Treg cell-originated TGF-ß levels were slightly lower in patients with SAR compared to the controls, although the difference was not statistically significant (p=0.178, p=0.296; respectively). None of the above mentioned cytokine levels changed significantly as a result of SIT. CONCLUSION: The results of our study indicate that although clinical findings improve after one year of SIT, this duration may not be sufficient to detect changes in cytokine patterns and transcription factors. Further studies that evaluate outcome over a longer duration of treatment would provide valuable information.

Is pulmonary arterial pressure affected by allergic rhinitis with nasal obstruction?

Obstructive pathologies of the pulmonary tract may cause various levels of hypoxia. To compensate for the hypoxia, pulmonary arterial pressure and pulmonary arterial flow may increase. We investigated 35 patients with seasonal allergic rhinitis (AR) whether hypoxia caused by AR with a high level of obstruction in the airways may lead to an increased pulmonary arterial pressure. An echocardiographical evaluation was made following the determination of the symptomatic and non-symptomatic symptom scores. We found a positive correlation between the symptom scores both in the symptomatic and non-symptomatic periods, nasal obstruction scores and the mean pulmonary arterial pressures during these periods. Further studies with more cases are needed in order to determine the cardiac effects of hypoxia in AR, mainly pulmonary arterial hypertension.

Effects of glucan treatment on the Th1/Th2 balance in patients with allergic rhinitis: a double-blind placebo-controlled study.

BACKGROUND: Allergic rhinitis (AR) is a disease characterized by IgE-mediated, allergic inflammation of the nasal mucosa. T helper (Th) 2 cells play an important role in the development of IgE-mediated diseases such as AR, with local overproduction of Th2 cytokines (IL-4, IL-5 and IL-13) at the site of allergic inflammation. Th1 cytokines (IL-12 and IFN-gamma) are known to suppress this Th2 immune response, aiding the treatment of these diseases. Beta-1,3-1,6-glucan (Glucan) is an immunomodulator stimulating particularly the antitumor response. An efficient antitumor stimulation can be achieved through a Th1-mediated immune response. OBJECTIVE: The aim of this study was to investigate the effects of Glucan on the immunopathogenic processes in the microenvironment to determine if it reverses the Th2-mediated immune response in AR to Th1-mediated response. METHODS: 24 Olea europea mono-sensitized patients with AR were randomized into Glucan and placebo groups. The Glucan group consisted of 12 patients who received Glucan treatment for 12 weeks, while the placebo group of 12 patients received placebo during the same period. A nasal provocation test (NPT) with Olea europea was performed at the beginning and end of treatment, and nasal lavage followed the positive NPT. IL-4, IL-5, IFN-gamma and IL-12 levels and the eosinophil count (%) were measured in nasal lavage fluid (NLF) samples. Simultaneously, peripheral blood eosinophil % values were measured. RESULTS: After treatment, IL-4 and IL-5 levels in NLF from the Glucan group were found to have decreased significantly (p = 0.027, p = 0.04; respectively), while IL-12 levels were found to have significantly increased (p = 0.008). However, IFN-gamma levels had not changed. On the other hand, none of the cytokine levels had changed significantly in the placebo group following treatment. Moreover, the percentage of eosinophils in the NLF was found to have decreased significantly after treatment in the Glucan group (p = 0.01), while that of the placebo group did not change. Peripheral blood percentage eosinophil levels had not changed significantly in any group. CONCLUSION: Th2-originated IL-4 and IL-5 levels responsible for the allergic inflammatory response in the microenvironment of patients with AR, are decreased with Glucan while levels of Th1-originated IL-12 are increased. Moreover, eosinophils, which are important effector cells of the inflammatory response, are decreased in the microenvironment. As a result, Glucan may have a role as an adjunct to standard treatment in patients with AR.

Sexual dysfunction in patients with allergic rhinoconjunctivitis.

BACKGROUND: Sexual dysfunction in chronic diseases has recently attracted attention owing to its impact on quality of life (QoL). Allergic rhinoconjunctivitis (ARC) affects QoL, causing limitations in many areas. However, there has not been research on changes in sexual function in patients with ARC. OBJECTIVE: To report the effect of ARC and its treatment on sexual function in men and women. METHODS: Forty-three sexually active patients with seasonal ARC aged 22 to 49 years were included in the study. The control group was composed of 40 healthy individuals aged 22 to 46 years. Conjunctival symptom scores (CSSs) and nasal symptom scores (NSSs) of patients with symptomatic ARC were determined, as were sexual function scores (SFSs) using the Female Sexual Function Index and the International Index of Erectile Function during allergen exposure in the pollination period and after treatment with oral desloratadine, 5 mg/d, for 30 days. The SFSs were evaluated in the control group. RESULTS: The CSSs and NSSs significantly improved in treated ARC (P < .001). In women, Female Sexual Function Index results in symptomatic ARC were significantly lower than in treated ARC and controls (P = .003). In men, International Index of Erectile Function results in treated ARC (P = .001) and controls (P < .001) were significantly higher than in symptomatic ARC. Furthermore, correlation between improvement in CSSs and NSSs and that of SFSs was determined (P = .007 for women; P = .001 for men). CONCLUSION: Improvement in sexual function as a variable of QoL may accompany the treatment of symptoms in patients with ARC.

Serum transforming growth factor-beta1(TGF-beta1) in patients with cirrhosis, chronic hepatitis B and chronic hepatitis C [corrected].

Chronic liver disease and cirrhosis are two of the most important health problems according to current gastroenterology literature. Based on the recent developments in the field of immunology, advanced follow-up and treatment modalities have been introduced for these disorders. Immune defence against viral infections depends on effective cellular immune responses derived mainly from Th1-related cytokines. Th2 type immune responses can inhibit efficient immune function by secretion of several cytokines such as IL-10, TGF-beta1. In this particular study, we determined the serum levels of TGF-beta1, which plays a role in immune suppression and induction of tissue fibrosis. We evaluated the role of TGF-beta1 in the pathogenesis of chronic liver disease and cirrhosis. Fourteen chronic hepatitis B (CHB), 12 chronic hepatitis C (CHC) patients and 21 cirrhotic patients were enrolled in the study. The control group consisted of ten healthy people. Serum TGF-beta1 levels were higher in both cirrhosis and CHC group when compared to those in CHB and control groups (P < 0.05). Although serum TGF-beta1 levels in the cirrhosis group were higher than that in the CHC group, the difference was not statistically significant. In conclusion, elevated TGF-beta1 levels in patients with CHC and cirrhosis may have a role in the pathogenesis and chronicity of these diseases.

Is the menstrual cycle affecting the skin prick test reactivity?

Allergen skin prick tests (SPT) are very sensitive and specific tests to detect allergic sensitization in atopic patients. Certain factors like antihistamines, antidepressant therapies or circadian rhythms can alter the results of SPT. In women, the changes in endogenous hormone levels throughout the menstrual cycle may affect the allergic responses and natural course of allergic diseases. The aim of this study was to investigate the probable influence of the phases of the menstrual cycle on SPT reactivity to allergen extracts and histamine. Forty-two female patients with seasonal allergic rhinoconjunctivitis were enrolled in the study. Skin prick test reactivities to allergens and histamine were measured at the beginning of the menstrual cycle (3rd or 4th day), mid-cycle (14th or 15th day) and end-cycle (27th or 28th day) consecutively. Serum estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were determined simultaneously. We observed the most significant reactions to allergens when SPT is performed at mid-cycle. However, SPT reactivity to histamine did not vary throughout the menstrual cycle. Serum estradiol and LH levels showed positive correlation with SPT reactivity to allergens at mid-cycle. Our results suggest that SPT give the best results when they are performed at mid-cycle. Additionally, allergens seem to cause mast cell degranulation to a greater extent in subjects in which endogenous hormones like estradiol and LH are elevated.

Increased expression of angiogenic markers in patients with seasonal allergic rhinitis.

BACKGROUND: Increased vascularity due to neo-angiogenesis is an essential part of airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway remodelling has been documented in asthma but not in allergic rhinitis. OBJECTIVE: We aimed to investigate the presence of increased angiogenesis and its relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three different immunohistochemical analysis methods, namely HSCORE, microvessel density (MVD) and vascular surface density (VSD). The findings in allergic rhinitis were compared with the findings in nasal septal deviation (NSD), which is not associated with increased angiogenesis. METHODS: Twenty patients with symptomatic SAR, who were not under treatment, were enrolled in the study. Ten patients with NSD, who needed surgical therapy, served as the control group. Demographic characteristics did not differ between the two groups. Inferior turbinate biopsy was obtained from SAR patients and control patients, under local anaesthesia and during surgery respectively. All biopsies were evaluated for angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using three immunohistochemical analysis methods (HSCORE, MVD and VSD).Results. HSCORE, estimated on the basis of each staining technique, showed statistically significant differences among the two groups (p=0.002; p=0.045; p=0.016, respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when compared to the controls (p=0.038; p=0,009, respectively). No statistically significant difference was found in Anti-FvW-based MVD between SAR patients and controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy specimens displayed a statistically significant difference between the two groups (p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not significantly different between the groups (p=0.086). On the other hand, morphometric data obtained by all three methods did not correlated. CONCLUSION: There are a few studies that have investigated the essential role of angiogenesis in the pathogenesis of allergic rhinitis. We conclude that, increased angiogenesis may be as prominent in patients with allergic rhinitis as in patients with non-allergic nasal pathologies and may play an important role in the remodelling of nasal mucosa of subjects with SAR.