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Biomedical subjects

S Rak

Publications and source records attributed to S Rak.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients.

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.

Administration, Inhalation↗
PubMed2000

Demonstration of mast cell chemotactic activity in bronchoalveolar lavage fluid collected from asthmatic patients before and during pollen season.

BACKGROUND: Mast cells are versatile effector cells of primary importance in asthma and airway inflammation. During inflammation mast cells accumulate in the bronchial epithelium. The mechanism for this increase in mast cell number has not been defined. OBJECTIVES: The aim of this study was to examine the presence of mast cell chemotactic activity in bronchoalveolar lavage (BAL) fluid taken before and at the end of 2 pollen seasons from patients with allergic asthma. METHODS: To measure mast cell chemotactic activity, we used a modified Boyden chamber and the human mast cell line HMC-1 or in vitro-developed mast cells as responder cells. RESULTS: A total of 27 patients were investigated, of which 8 exhibited mast cell chemotactic activity in their BAL fluid collected before season. A significant increase in the activity was found in 18 of 27 BAL fluids sampled at the end of the pollen season. No difference was found between patients treated with immunotherapy or placebo. The presence of stem cell factor could be detected in all BAL fluids analyzed. Blocking antibodies against stem cell factor or transforming growth factor-beta partially blocked the activity in some of the BAL fluids. Treatment of the responder cells with pertussis toxin reduced the migratory activity in 13 of 14 BAL fluids collected during pollen season. CONCLUSION: This study demonstrates the presence of mast cell chemotactic activity in BAL fluids from patients with allergic asthma, with a significant increase in activity during pollen season. The major part of this activity consisted of factors mediating their effect through G(i)-protein coupled receptors. This activity may be responsible for the mast cell accumulation in the intraepithelial layer seen in allergic asthmatic patients.

Asthma↗
PubMed2000

Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis is a common condition often requiring treatment. OBJECTIVE: We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant humanized construct of a murine antibody that binds to circulating IgE, could control symptoms and reduce intake of concomitant medication in seasonal allergic rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule predicted to reduce serum free IgE levels below 25 ng/mL. METHODS: We randomly assigned 251 adult subjects with a history of SAR and a positive skin test response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 times during the season, depending on baseline IgE levels. The primary efficacy variable was the subject's average daily nasal symptom severity score (sneezing, itching, runny, and stuffy nose) from diary data collected over the double-blind treatment period. Secondary efficacy variables included the average number of rescue antihistamine tablets per day, the proportion of days with any SAR medication use, and rhinoconjunctivitis-specific quality of life (QOL). RESULTS: Significant between-treatment differences in favor of rhumAb-E25 were observed in average daily nasal symptom severity scores, the average number of tablets of rescue antihistamines per day, the proportion of days with any SAR medication use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb-E25-treated subjects and were associated with clinical effectiveness. Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were detected. CONCLUSION: Compared with placebo, rhumAb-E25 was safe and effective in controlling birch pollen-induced SAR symptoms, with less concomitant medication use and improved QOL. This study shows the therapeutic potential of anti-IgE antibody in SAR.

Adolescent↗
PubMed1999

Cellular infiltration and cytokine mRNA expression in perennial allergic rhinitis.

BACKGROUND: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2-type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast-cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T-cell and eosinophil infiltration of the nasal mucosa, local Th2-type cytokine expression, and increased numbers of nasal epithelial mast cells. METHODS: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA-expressing cells. RESULTS: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase-positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)-5 were higher (P=0.01) and the numbers of cells expressing IL-2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL-4 or interferon-gamma between the groups. CONCLUSIONS: Perennial allergic rhinitis is characterized by mast-cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T-cell cytokine production in favour of enhanced IL-5 and reduced IL-2 expression.

Adult↗
PubMed1999

Inflammatory cell populations and cytokine mRNA expression in the nasal mucosa in aspirin-sensitive rhinitis.

Aspirin-sensitive rhinitis is characterized by severe perennial nasal congestion and discharge. The study questioned whether this disease, like immunoglobulin E-mediated rhinitis, might be associated with local recruitment and activation of T-lymphocytes, mast cells and eosinophils with parallel increases in "T-helper2-type" cytokines. Nasal biopsies from 10 patients with aspirin-sensitive rhinitis and 12 healthy controls subjects were studied. Nasal mucosal sections were examined by immunohistochemistry in order to determine cell phenotypes and by in situ hybridization to detect cells expressing messenger ribonucleic acid (mRNA) for cytokines. In aspirin-sensitive rhinitis there were increases in total (CD3+) (p=0.05) and activated (CD25+) T-cells (p=0.007), total (major basic protein (MBP) positive) (p=0.004) and activated (monoclonal antibody which recognizes the cleaved form of eosinophil cationic protein (EG2) positive) eosinophils (p=0.003), tryptase+ mast cells (p=0.04) and CD68+ macrophages (p=0.002). Neutrophils and cells expressing human leukocyte antigen-DR were no different. Marked increases were observed in the numbers of interleukin (IL)-5 mRNA+ cells (p=0.004) in aspirin-sensitive patients, whereas lower numbers of IL-4 mRNA+ cells were observed, with a trend for a difference from controls (p=0.07). No differences were observed for either IL-2 or interferon-gamma. In conclusion, in aspirin-sensitive rhinitis there is intense inflammation of the nasal mucosa characterised by T-lymphocytes, eosinophils and mast cells. The predominance of macrophages and disproportionate increase in interleukin-5 compared to interleukin-4 messenger ribonucleic acid expression suggests that factors other than "allergic" mechanisms may be important in this disease.

Adult↗
PubMed1999

The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung.

BACKGROUND: Bronchoalveolar lavage (BAL) fluid from patients with birch-pollen allergy lavaged during the season showed an elevated chemotactic activity for eosinophils compared with BAL fluid from the same patients before the start of the season. AIM: The aim of this study was to identify the eosinophil chemotactic agents in the BAL fluid, to compare these findings with in vitro studies on selected cytokines, and to investigate the interactions between these cytokines. METHODS: Neutralizing antibodies for interleukins (IL) -2, -5 and -8, RANTES and leukaemia inhibitory factor (LIF) were added to the BAL fluid, and the chemotactic activity was tested with eosinophils from allergic donors. Eosinophils from healthy donors were preincubated with IL-5 in order to mimic the primed state of eosinophils from allergics, and the migration towards recombinant IL-5, IL-8, and RANTES in different combinations was measured. Eosinophils from allergic donors were also used. RESULTS: Anti-IL-5, anti-IL-8 and anti-RANTES inhibited the chemotactic activity in the BAL fluid. Recombinant RANTES induced migration, which was enhanced by preincubation of the cells with IL-5. Only eosinophils from symptomatic allergics responded to IL-8, and IL-5 was not sufficient to prime normal eosinophils in vitro to an IL-8 response. A negative correlation was found between the level of in vivo activation of the cells and their response to IL-5, and a positive correlation with the response to RANTES. CONCLUSION: IL-8 and RANTES are important for eosinophil accumulation to the lung of pollen-allergic asthmatics. IL-5 alone may not be responsible for the priming of eosinophils in vivo, but is an essential cofactor for the other chemoattractants.

Adult↗
PubMed1998

Activation of B-lymphocytes during pollen season. Effect of immunotherapy.

BACKGROUND: B-lymphocytes play an important part in the allergic reaction as producers of IgE antibodies. OBJECTIVE: To investigate the cell surface expression of the activation antigens CD23, CD40 and HLA-DR on B-lymphocytes in birch pollen allergic patients before and during birch pollen season and to study the effect of immunotherapy. METHODS: The study included 24 birch pollen allergic patients half of whom were treated with immunotherapy against birch pollen before the start of the season. Eleven of the 24 patients had asthma. Blood samples were taken and lung function was registered before the season began and before the immunotherapy treatment in January to February and during the season in May. The relative number of B-lymphocytes (CD19+) of the lymphocyte population and the cell surface expression of CD23, CD40 and HLA-DR on B-lymphocytes was measured by the use of flow cytometry. RESULTS: In the control group of patients the relative number and concentration of B-lymphocytes, the cell surface expression of CD23, CD40 and HLA-DR on B cells, and the serum concentration of IgE increased during season compared with before season. In contrast, in the immunotherapy treated patients no changes in the number of B cells or cell surface expression of CD23, CD40 and HLA-DR were demonstrated. CONCLUSION: The elevated expression of CD23, CD40 and HLA-DR on B cells, combined with increased levels of IgE in allergic patients during season could be explained by the effect of cytokines produced by activated TH2 cells. A shift from TH2 to TH1 cells might be the mechanism after the absence of signs of B-cell activation in immunotherapy treated patients. The prevention of increased cell surface expression on B cells by immunotherapy may constitute a significant mechanism behind the beneficial effects of immunotherapy in the treatment of pollen atopy.

Adult↗
PubMed1998

Increased frequencies of allergen-induced interleukin-13-producing cells in atopic individuals during the pollen season.

We have reported previously that allergen-specific serum IgE levels were correlated with allergen-induced interleukin (IL)-4 in type I allergic individuals. Here, we wanted to investigate whether IL-13, another switch factor for IgE, was induced by allergen in vitro and if so, whether this was correlated with the elevated serum IgE-levels seen in atopic individuals, and whether the cytokine profile changed during pollen season. Peripheral blood mononuclear cells from 14 atopic and 14 healthy individuals collected out of the pollen season were incubated in vitro with allergens (birch or timothy) and the number of IL-4, IL-13, IL-10 and IFN-gamma producing cells was determined by ELISPOT. In response to the specific allergen, IL-13-producing cells were seen in allergic but not in healthy individuals. The number of IL-13-producing cells was significantly correlated with the allergen-specific serum IgE levels. When the allergic individuals were tested during the pollen season, the number of allergen-specific IL-4- and IL-13-producing cells, as well as serum levels of specific IgE, increased. The IL-13 increase seen in ELISPOT was confirmed by a RT-PCR assay. No seasonal changes were seen in response to purified protein derivative (PPD) or the mitogen PHA. During the pollen season, the IL-4 and IL-13 responses were highly correlated. Taken together, our results support the roles of both IL-13 and IL-4 in the regulation of allergen-specific IgE levels in atopic individuals.

Aged↗
PubMed1998

Blood eosinophils from asymptomatic allergics have a reduced capacity to produce oxygen-free radicals.

BACKGROUND: The eosinophil granulocyte is an inflammatory cell that plays an active part in diseases such as asthma and rhinitis. This study aimed to investigate oxidative metabolism by blood eosinophils taken from allergic rhinitis patients, asthmatics, and nonallergic controls before and during the birch-pollen season. METHODS: Twenty patients with allergy to birch pollen and seasonal symptoms of rhinitis, some of whom were also asthmatic, were followed before and during the birch-pollen season in Sweden. The cells were purified using a Percoll gradient and the MACS system. Eosinophil purity in all samples was > 95%. Oxidative metabolism was measured by a chemiluminescence (CL) assay, with luminol and lucigenin acting as enhancers, and PMA, serum-treated zymosan (STZ), interleukin (IL)-5, or RANTES as stimuli. RESULTS: The allergic subjects showed reduced luminol CL when activated before the season with PMA (P = 0.040) or STZ (P = 0.0055). This was not seen during pollen exposure. STZ-activated lucigenin CL was also reduced before the season (P = 0.0027). The reduction was most evident in the group with asymptomatic rhinitis. In terms of eosinophil stimulation, IL-5 and RANTES were equally effective in allergic and nonallergic subjects, both before and during the pollen season. CONCLUSIONS: Blood eosinophils from asymptomatic allergics may have a lower capacity to produce oxygen-free radicals than eosinophils from nonallergics.

Acridines↗
PubMed1998

Allergen-specific increase in interleukin (IL)-4 and IL-5 secretion from peripheral blood mononuclear cells during birch-pollen immunotherapy.

The mechanisms behind the effects of immunotherapy (IT) with birch-pollen extract are largely unknown. In this pilot study, we measured the cytokine secretion in vitro from peripheral blood mononuclear cells (PBMC) obtained from birch-pollen-allergic patients undergoing IT treatment (n = 4) or placebo administration (n = 4), collected before treatment, 1 and 4 weeks after start of treatment, and during and just after the pollen season (12-14 weeks after start of treatment). The PBMC were stimulated with birch-pollen extract in vitro for 7 days, followed by restimulation with the mitogens phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) for 24 h, to enhance the production of cytokines. The supernatants were analyzed with ELISA and radioimmunoassay for interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-5. In the therapy group, we noted an increased secretion of IL-4 and IL-5 from PBMC collected at 4 weeks after the start of treatment (IL-4: 29 +/- 21 pg/ml [day 0] to 374 +/- 448 pg/ml [week 4], mean +/- SD; IL-5: 95 +/- 48 pg/ml to 1147 +/- 697 pg/ml). No increase was seen in the placebo group. During the pollen season, we noted a trend toward increased IL-4 and IL-5 secretion in both groups. We conclude that the temporary increase in serum IgE observed in many IT studies may be a consequence of increased IL-4 production due to the allergen exposure.

Adult↗
PubMed1998

Granulocyte/macrophage-colony stimulating factor in allergen-induced rhinitis: cellular localization, relation to tissue eosinophilia and influence of topical corticosteroid.

BACKGROUND: Allergen-induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2-type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage-colony stimulating factor (GM-CSF) may contribute to late-responses and tissue eosinophilia and is inhibitable by topical corticosteroid. METHODS: Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM-CSF. RESULTS: Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5-fold increase in cells expressing mRNA for GM-CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM-CSF mRNA+ cells were co-localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM-CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM-CSF. CONCLUSIONS: The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM-CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM-CSF from T lymphocytes or reducing autocrine production of GM-CSF from eosinophils.

Administration, Intranasal↗
PubMed1998

Repeated exposure to an ambient level of NO2 enhances asthmatic response to a nonsymptomatic allergen dose.

We investigated the effects of NO2 and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 microg x m(-3) NO2 for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO2 and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO2 was at EP -25% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO2 exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO2 plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO2 enhances the airway response to a nonsymptomatic allergen dose.

Adult↗
PubMed1997

Allergen induced cytokine profiles in type I allergic individuals before and after immunotherapy.

Allergen immunotherapy (IT) involves subcutaneous injections of increasing doses of specific allergen over a period of time. It is recognised as highly effective in the treatment of patients with allergic rhinitis. However, the specific immunological mechanisms by which IT achieves its effect have not been fully elucidated. Recent studies, have shown that the clinical effects following IT of allergic individuals is concomitant with a reduced production of IL-4 by allergen specific CD4+ T-cells. The aim of the present study was to gain better knowledge about the immunological mechanisms by which IT exerts its beneficial effects. For this purpose, peripheral blood mononuclear cells (PBMC) from ten individuals receiving birch allergen or placebo in an IT-study performed in a double-blind manner, were analysed for IL-4, IFN-gamma, IL-5 and IL-10 mRNA expression at the onset of the study and during the pollen season, during treatment. Both spontaneous and in vitro allergen-induced cytokine mRNA expression was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR). Spontaneous expression of IL-4 mRNA could be detected in most of the allergic patients, but not in healthy donors. The IT-treated patients showed a decrease in the spontaneous expression of IL-4 mRNA during the pollen season as compared to at the onset of the study, while in patients receiving placebo the IL-4 mRNA expression increased or remained unchanged. Similar results were obtained after in vitro stimulation with allergen. This was in contrast to the results for IFN-gamma, which was readily detected in both patient groups with no significant differences between the groups at either timepoint. IL-5 was shown to be increased during the pollen season in both groups and thereby presumably not affected by allergen IT. Taken together, these observations suggest that the cytokine profiles in circulating T lymphocytes change as a consequence of allergen IT.

Allergens↗
PubMed1997

Expression of epsilon germ-line gene transcripts and mRNA for the epsilon heavy chain of IgE in nasal B cells and the effects of topical corticosteroid.

We have studied the expression of the gene encoding the epsilon heavy chain of IgE in nasal B cells of hayfever patients. We developed probes to detect transcripts of the epsilon germ-line gene and the rearranged gene by in situ hybridization of biopsy sections from the nasal mucosa. We compared tissue from hayfever patients out of season with that of normal controls, and also of hayfever patients treated with topical corticosteroid (fluticasone propionate) or placebo for 6 weeks and then challenged with antigen. epsilon chain mRNA was expressed in an unexpectedly high proportion of nasal B cells of both hayfever patients and normal subjects. However, although similar numbers of B cells were found in both groups, the proportion of cells that express epsilon chain mRNA was several times higher in the hayfever patients. No transcripts of the epsilon germ-line gene were detected in either group before allergen challenge. When hayfever patients were administered antigen locally, early (10-30 min) and late (1-24 h) symptoms ensued. After 24 h, coincident with an increase in the number of cells expressing mRNA for IL-4 in the tissue, epsilon germ-line gene transcripts appeared in the nasal B cells. The induction by allergen of IL-4 mRNA and epsilon germ-line gene transcripts was suppressed by fluticasone propionate treatment. Our results suggest that local IgE synthesis and cytokine regulation of heavy chain switching to IgE occur in the nasal mucosa.

Administration, Topical↗
PubMed1997

Priming of eosinophil adhesion in patients with birch pollen allergy during pollen season: effect of immunotherapy.

The adhesion of eosinophil granulocytes to E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) was investigated before and during birch pollen season in 24 patients allergic to birch pollen who had rhinoconjunctivitis and, in half of the cases, asthma during season. Half of the patients were undergoing specific immunotherapy for birch pollen allergy. Increased adhesion to VCAM-1 and ICAM-1 (p < 0.05) during season as compared with before season was demonstrated by eosinophils of patients in the control group and by eosinophils of the patients without asthma treated with immunotherapy, but not by eosinophils from the immunotherapy-treated patients with asthma. Eosinophils from the control group of patients demonstrated increased cell surface expression of CD18 and CD49d (p < 0.05 and p < 0.01, respectively) during season as compared with before season, and eosinophils from the immunotherapy-treated patients showed increased cell surface expression of CD49d (p < 0.01) during season. Simultaneous measurement of neutrophil adhesion revealed increased adhesion to E-selectin and ICAM-1 (p < 0.01) during season compared with before season in the immunotherapy-treated group of patients. Neutrophils from the control subjects without asthma showed increased adhesion to E-selectin (p < 0.05) during season. In conclusion, eosinophils from patients allergic to birch pollen demonstrated priming of the adhesion to VCAM-1 to ICAM-1 during birch pollen season. Immunotherapy treatment prevented the priming of eosinophil adhesion during pollen season in the patients allergic to birch pollen who had asthma, but not in those without asthma. In contrast, neutrophils from the immunotherapy-treated patients, both with and without asthma, demonstrated priming of the adhesion to E-selectin and ICAM-1 during season. The latter results indicate that immunotherapy, in case of the patients allergic to birch pollen with asthma induced a shift from the production of primarily eosinophil priming agents to primarily neutrophil priming agents, which may be caused by a shift from Th2 to Th1 lymphocytes.

Adult↗
PubMed1997

Expression of IL-16 in allergen-induced late-phase nasal responses and relation to topical glucocorticosteroid treatment.

Allergen-induced late nasal responses (LNRs) are associated with a cellular infiltrate in which CD4+ cells are prominent. These cells have been shown to be the major cellular source of Th2-type cytokines. Mechanisms responsible for the local accumulation of CD4+ cells in the nasal mucosa after allergen exposure are unclear. IL-16 is a potent chemoattractant for CD4+ cells in vitro and may play a significant role in recruiting CD4+ cells in LNRs. We investigated the expression of IL-16 messenger RNA and immunoreactivity in nasal biopsy specimens from 17 subjects with allergic rhinitis. A biopsy specimen of the nasal inferior turbinate was obtained before and 24 hours after local nasal provocation with grass pollen extract after 6 weeks of treatment with either topical fluticasone propionate (n = 9) or placebo (n = 8) nasal spray twice daily. IL-16 mRNA-positive cells and IL-16-immunoreactive cells were identified in both the epithelium and the subepithelial tissue at baseline. Within the placebo-treated group, the numbers of epithelial and subepithelial IL-16 mRNA-positive cells and IL-16-immunoreactive cells were significantly increased 24 hours after challenge compared with baseline (p < 0.001). Topical glucocorticoid therapy resulted in a decrease in allergen-induced epithelial immunoreactive cells and subepithelial IL-16 mRNA-positive cells. The numbers of CD4+ cells increased after antigen challenge compared with baseline (p < 0.05), and this increase was inhibited by glucocorticoid treatment. There were significant correlations between epithelial and subepithelial IL-16 immunoreactivity and CD4+ cell infiltration after antigen challenge. The upregulation of IL-16 expression in allergic nasal mucosa after antigen challenge may have critical implications in the accumulation of CD4+ cells in response to antigen exposure. Steroid-mediated inhibition of IL-16 may be partly responsible for the decrease in local CD4+ cells after topical glucocorticoid therapy.

Administration, Topical↗
PubMed1997

An intranasal glucocorticoid inhibits the increase of specific IgE initiated during birch pollen season.

BACKGROUND: Recent in vitro findings show that glucocorticoids in combination with IL-4 can induce the synthesis of IgE, indicating that glucocorticoids may promote allergy. OBJECTIVE: A double-blind, placebo-controlled study was performed to evaluate the effect of an intranasal glucocorticoid on the levels of birch pollen-specific IgE antibodies in serum from patients with allergic rhinitis. METHODS: Eighteen patients with allergic rhinitis received treatment with an intranasal glucocorticoid (beclomethasone dipropionate, 400 microg/day) or placebo for 5 weeks, starting from the beginning of the birch pollen season. Blood samples for anti-birch IgE evaluation were taken before treatment was initiated and at 2 and 5 weeks after the beginning of the study. RESULTS: The beclomethasone group (n = 9) had significantly lower symptom scores when compared with the placebo group (n = 9) (0.86 +/- 0.26 vs 2.79 +/- 0.76, p value = 0.01). Both the treatment group and the placebo group showed a trend of an increase in anti-birch IgE levels 2 weeks after the beginning of the treatment (from 33.1 +/- 13.1 kU/L to 44.9 +/- 20.9 kU/L in the beclomethasone group and from 53.2 +/- 18.9 kU/L to 64.1 +/- 22.1 kU/L in the placebo group). Treatment with beclomethasone returned anti-birch IgE levels to baseline by the end of the study, whereas in the placebo group the anti-birch IgE levels continued to increase (final values, 33.1 +/- 11.9 kU/L vs 72.6 +/- 23.2 kU/L, respectively). The change in IgE antibody levels in the placebo group was significantly higher than that in the beclomethasone group. No statistically significant changes in total IgE or soluble CD23 levels were detected. CONCLUSION: We conclude that treatment with an intranasal glucocorticoid initiated at the beginning of the pollen season inhibits the induced increase in specific IgE.

Administration, Intranasal↗