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Stephen C Dreskin

Publications and source records attributed to Stephen C Dreskin.

14 recordsLinked to original sources
PubMed2006

Effect of thymoquinone on cyclooxygenase expression and prostaglandin production in a mouse model of allergic airway inflammation.

Prostaglandins (PGs) are potent proinflammatory mediators generated through arachidonic acid metabolism by cyclooxygenase-1 and -2 (COX-1 and COX-2) in response to different stimuli and play an important role in modulating the inflammatory responses in a number of conditions, including allergic airway inflammation. Thymoquinone (TQ) is the main active constituent of the volatile oil extract of Nigella sativa seeds and has been reported to have anti-inflammatory properties. We examined the effect of TQ on the in vivo production of PGs and lung inflammation in a mouse model of allergic airway inflammation. Mice sensitized and challenged through the airways with ovalbumin (OVA) exhibited a significant increase in PGD2 and PGE2 production in the airways. The inflammatory response was characterized by an increase in the inflammatory cell numbers and Th2 cytokine levels in the bronchoalveolar lavage (BAL) fluid, lung airway eosinophilia and goblet cell hyperplasia, as well as the induction of COX-2 protein expression in the lung. Intraperitoneal injection of TQ for 5 days before the first OVA challenge attenuated airway inflammation as demonstrated by the significant decrease in Th2 cytokines, lung eosinophilia, and goblet cell hyperplasia. This attenuation of airway inflammation was concomitant to the inhibition of COX-2 protein expression and PGD2 production. However, TQ had a slight inhibitory effect on COX-1 expression and PGE2 production. These findings suggest that TQ has an anti-inflammatory effect during the allergic response in the lung through the inhibition of PGD2 synthesis and Th2-driven immune response.

Allergens↗
PubMed2006

Chronic urticaria sera increase basophil CD203c expression.

BACKGROUND: Approximately 40% of patients with chronic idiopathic urticaria have antibodies to the alpha subunit of the high-affinity IgE receptor. CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcepsilonRIalpha receptor and may serve as a useful marker to identify these patients. OBJECTIVE: The primary objective was to assess the affect of sera from patients with chronic idiopathic urticaria on basophil CD203c expression. Secondary objectives were to correlate CD203c expression with basophil histamine release and size of the autologous serum skin test and to determine whether the mechanism is mediated by an IgG antibody. METHODS: Sera were obtained from patients with chronic idiopathic urticaria and positive autologous serum skin test or negative autologous serum skin test and normal controls. Sera were incubated with donor whole blood. Activated basophils from whole blood were identified by flow cytometry on the basis of the presence of CD203c on high-expressing IgE positive cells. RESULTS: Incubation of donor basophils with sera from patients with chronic idiopathic urticaria and positive autologous serum skin test demonstrated significant upregulation of CD203c. IgG depletion of representative sera from patients with chronic idiopathic urticaria resulted in significant decrease in CD203c expression on donor basophils. CD203c expression correlated with basophil histamine release and the size of the autologous serum skin test. CONCLUSION: Sera from patients with chronic idiopathic urticaria and positive autologous serum skin test significantly upregulate basophil CD203c and correlate with basophil histamine release. CLINICAL IMPLICATIONS: This article describes an activation marker on basophils whose expression is increased by sera from patients with chronic idiopathic urticaria.

Adult↗
PubMed2006

Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma.

Chronic airway inflammation is a key feature of bronchial asthma. Leukotrienes are potent inflammatory mediators that play a role in the pathophysiology of asthma, and their levels are elevated in the airways in response to allergen challenge. We examined the anti-inflammatory effect of thymoquinone (TQ), the active principle in the volatile oil of Nigella sativa seeds, on leukotriene (LT) biosynthesis in a mouse model of allergic asthma. Mice sensitized and challenged with ovalbumin (OVA) antigen had an increased amounts of leukotriene B4 and C4, Th2 cytokines, and eosinophils in bronchoalveolar lavage (BAL) fluid. In addition, there was also a marked increase in lung tissue eosinophilia and goblet cell numbers. Administration of TQ before OVA challenge inhibited 5-lipoxygenase, the main enzyme in leukotriene biosynthesis, expression by lung cells and significantly reduced the levels of LTB4 and LTC4. This was accompanied by a marked decrease in Th2 cytokines and BAL fluid and lung tissue eosinophilia, all of which are characteristics of airway inflammation. These results demonstrate the anti-inflammatory effect of TQ in experimental asthma.

Animals↗
PubMed2006

Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation.

Thymoquinone (TQ), the main active constituent of the volatile oil extracted from Nigella sativa's seeds, has been reported to have an anti-inflammatory and immune stimulatory effect on bronchial asthma and inflammation. However, little is known about the factors and mechanisms underlying these effects. In the present study, we examined the effect of TQ on airway inflammation in a mouse model of allergic asthma. Intraperitoneal injection of TQ before airway challenge of ovalbumin (OVA)-sensitized mice resulted in a marked decrease in lung eosinophilia and the elevated Th2 cytokines observed after airway challenge with OVA antigen; both in vivo, in the bronchoalveolar lavage (BAL) fluid and in vitro, following stimulation of lung cells with OVA. TQ also decreased the elevated serum levels of OVA-specific IgE and IgG1. Histological examination of lung tissue demonstrated that TQ significantly inhibited allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells. While TQ showed a significant effect in inhibiting IL-4, IL-5 and IL-13 and some effect in inducing IFN-gamma production in the BAL fluid, it did show a slight effect on in vitro production of IL-4 by cultured lung cells stimulated with OVA antigen. These data suggest that TQ attenuates allergic airway inflammation by inhibiting Th2 cytokines and eosinophil infiltration into the airways; thus demonstrating its potential anti-inflammatory role during the allergic response in the lung.

Allergens↗
PubMed2006

Genetics of food allergy.

Allergic reactions to foods are an important medical problem throughout the industrialized world. The occurrence of food allergy appears to be strongly influenced by genetics, but the basis of the genetic predisposition to food allergy has not been differentiated from that for atopy in general. In addition, genetic susceptibility alone does not explain the prevalence of food allergy satisfactorily, leaving ample room to consider the importance of environmental influences (external, maternal, and gastrointestinal environment) and interactions between the host and the environment. Several features of food allergy are highlighted in this review: 1) patients with severe food allergies are overwhelmingly atopic, but food allergy occurs only in approximately 10% of patients with other atopic diseases; 2) most patients are clinically reactive to a single food, and although a substantial minority have multiple food allergies, the variety of bone fide food allergies in a given individual is limited; 3) foods contain multiple proteins whereas only a small subset are allergenic; 4) there is likely an important contribution of the environment, becoming manifest in genetically susceptible individuals.

Environmental Exposure↗
PubMed2005

Comparative potency of Ara h 1 and Ara h 2 in immunochemical and functional assays of allergenicity.

To assess the relative potency of the major peanut allergens, Ara h 1 and Ara h 2, we examined the relative ability of purified proteins to bind IgE on immunoblots, to cross-link allergen specific IgE in an in vitro assay of degranulation based on RBL SX-38 cells, and to bind IgE in the ImmunoCap assay. Sera from 12 highly sensitive, peanut allergic patients were studied in all assays. IgE immunoblots with crude peanut extracts showed binding of IgE to multiple bands including the 63 kDa and 17-19 kDa bands that contain Ara h 1 and Ara h 2, respectively. In the functional assay, Ara h 2 was more potent than Ara h 1 in 11 of 12 sera tested with a median potency that was 52.5-fold more than Ara h 1 (P < 0.005). Contrary to findings with the functional assay, IgE immunoblots with purified Ara h 1 and Ara h 2 showed substantially lighter binding of IgE to Ara h 2 compared with Ara h 1 (P = 0.02). The ImmunoCap assay gave intermediate results with slightly more IgE binding to Ara h 2 than to Ara h 1 (P = 0.005). In conclusion, Ara h 2 is a very potent allergen and is much more potent than Ara h 1 for most sera using an in vitro assay of IgE cross-linking and cell activation. This finding is different from what was predicted based on immunoblots or with the ImmunoCap assay.

2S Albumins, Plant↗
PubMed2005

The thyroid and urticaria.

PURPOSE OF REVIEW: Although it is generally accepted that thyroid autoimmunity is more prevalent in patients with chronic urticaria than in the general population, the importance of this finding is unclear. In addition, there are reports that chronic urticaria remits in some but not all patients who have evidence of thyroid autoimmunity and are treated with l-thyroxine. This review will summarize the history of this controversy and suggest a possible role for thyroid autoimmunity in the pathophysiology of chronic urticaria. RECENT FINDINGS: Important subsets of patients with chronic urticaria have autoantibodies to the high-affinity receptor for IgE (FcepsilonRI), anti-IgE, and antithyroid antibodies. Patients with chronic urticaria and biochemical evidence of thyroid autoimmunity may have active thyroid disease or may be clinically euthyroid. These patients are often poorly responsive to conventional therapy of urticaria and may have more chronic disease. New findings on the pathogenic effects of anti-FcepsilonRI auto-antibodies and of antithyroid antibodies have revealed a role for complement activation. SUMMARY: Currently, there are no compelling arguments to decide whether or not thyroid autoimmunity plays a significant role in the pathogenesis of chronic urticaria. New developments concerning a role for complement activation in the pathogenesis of chronic urticaria may, however, lead to better understanding of this phenomenon in the future.

Alopecia Areata↗
PubMed2004

Urticaria and angioedema: an overview.

Persistent or frequent episodes of urticaria are difficult to evaluate and treat. The best test to identify most patients with a specific underlying cause (eg, physical trigger, allergen, systemic disease) likely is the taking of a careful and detailed history and performance of a physical examination by a specialist who is knowledgeable in urticarial disease. Further study of the pathogenesis and treatment of urticaria is crucial. Given the limited efficacy of presently approved antihistamine treatments and the significant side effects of steroids and cyclosporine, there is a pressing need to evaluate other anecdotally supported urticaria treatments in randomized, controlled trials.

Angioedema↗
PubMed2004

Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract.

BACKGROUND: The immunologic response to allergen immunotherapy with 3 serial 5-fold doses of cat extract has been studied after approximately 5 weeks of immunotherapy. The highest dose containing 15 mug of Fel d 1 produced the most consistent and favorable response. It is unknown whether the comparative response on reaching a maintenance dose is maintained with long-term maintenance therapy. OBJECTIVE: The purpose of this investigation was to evaluate the immunologic responses with these 3 serial doses of cat hair and dander extract at baseline, after reaching the maintenance dose (approximately 5 weeks), and after 1 year of maintenance immunotherapy. METHODS: Twenty-eight patients with cat allergy randomized in a double-blind study were assigned to one of 4 treatment groups: placebo or cat hair and dander extract containing 0.6 mug of Fel d 1, 3 mug of Fel d 1, and 15 mug of Fel d 1 at maintenance. Studies included skin prick tests and late cutaneous reactions with cat hair and dander extract, titrated nasal challenges with the extract, serum cat allergen-specific IgG4 and IgE measurement, and flow cytometric and ELISA analysis of whole blood and intranasal cytokines (TGF-beta, IL-10, IFN-gamma, IL-4, and IL-5). RESULTS: Twenty-six subjects completed the study. After both 5 weeks and 1 year, significant and dose-dependent differences were seen with total symptom scores on nasal challenge ( P < .0001), with titrated skin prick testing with cat dander extract at 5 weeks ( P = .014) and 1 year ( P < .0001), and with cat-specific IgG4 measurement at 5 weeks ( P = .004) and 1 year ( P = .003). At 1 year, neither flow cytometry of whole blood nor ELISA evaluation of nasal cytokines demonstrated any significant differences among the treatment groups. CONCLUSION: The response to titrated nasal allergen challenge, titrated skin prick testing, and allergen-specific IgG4 measurement to cat immunotherapy at 5 weeks is predictive of the response at 1 year.

Allergens↗
PubMed2003

RBL cells expressing human Fc epsilon RI are a sensitive tool for exploring functional IgE-allergen interactions: studies with sera from peanut-sensitive patients.

Rat basophilic leukemia cells (RBL SX-38) express the alpha, beta, and gamma chains of human Fc epsilon RI. Following sensitization with IgE from a subset of allergic human donors, these cells can be triggered by exposure to anti-IgE or to very low concentrations of specific allergens. We examined 18 sera from patients who were highly sensitive to peanuts by history and had anti-peanut IgE by in vitro testing. The ability of these sera to sensitize the RBL SX-38 cells for degranulation with peanut allergens correlates very well with the absolute amount of anti-peanut IgE (r=0.95; p<0.001). The most effective sera contained at least 50 kU/l of total IgE and at least 15 kU/l of peanut-specific IgE. RBL SX-38 cells sensitized with these sera degranulated optimally upon exposure to anti-IgE (net degranulation of 40+/-8%, means+/-S.D.; n=8) and to a 10(5)-10(6) dilution of crude peanut extract (CPE) (37+/-7% net degranulation; 93+/-13% of that seen with anti-IgE). This assay is quite sensitive. Cells sensitized with selected sera are activated by exposure to a 1:10(7) dilution of the CPE containing picogram amounts of peanut allergens. This assay is also quite specific. Cells sensitized with sera from patients with anti-peanut IgE and no detectable IgE against soybean, walnut or grass pollen did not degranulate following exposure to these latter antigens. The converse was also true; cells sensitized with sera from patients without anti-peanut IgE did not react to peanut. These data demonstrate that RBL cells expressing human Fc epsilon RI form the basis of a useful model system for the detection of allergens and for the study of IgE-allergen interactions.

Adult↗
PubMed2002

Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal epithelium taken from patients undergoing nasal allergen challenge.

Nasal allergen challenge of patients with allergic rhinitis results in increased numbers of inflammatory cells and increased production of pro-inflammatory cytokines including interleukin 5 (IL-5). We report a sensitive, noninvasive method to measure changes in the amount of mRNA for IL-5 in nasal epithelium and have used this method to detect alterations of IL-5 mRNA from patients undergoing a nasal allergen challenge. Ten grass or ragweed allergic adults were challenged out of season with appropriate pollen extracts at sufficient dose to give a rhinitis total symptom score of 5 on a scale of 12. After allergen exposure, symptoms were recorded hourly. At 0, 3, and 6 h after allergen exposure, secreted proteins were collected on filter paper strips and two superficial scrapings of nasal epithelium were obtained. The scrapings of epithelium were immediately immersed in 100 microl of RNAlater (Ambion, Austin, TX) and stored at 4 degrees C for up to 1 month without loss of RNA quality. Total RNA was isolated and RT-PCR was performed. cDNA for IL-5 was then measured by real-time fluorescence quantitative PCR with Pre-Developed TaqMan Assay Reagents (PE Biosystems, Foster City, CA). Sufficient RNA was isolated from eight subjects to measure IL-5 mRNA. Data were normalized for content of ribosomal RNA. The relative amount of cDNA for IL-5 was calculated by comparison with internal standards prepared from phytohemagluttinin-stimulated peripheral blood mononuclear cells. Messenger RNA for IL-5 was increased 8.7+/-2.7-fold at 3 h (p<0.01) and 39.5+/-20.9-fold at 6 h (p<0.01). Increased IL-5 mRNA levels at 6 h closely correlate with total symptom scores at 6 h (r=0.88; p=0.007). IL-5 protein was measured by ELISA in eluates from the filter papers. At 6 h, there was increased IL-5 protein (7.7+/-2.8 ng/ml) compared with time zero (1.8+/-0.5 ng/ml) (p=0.02). The levels of IL-5 protein did not correlate significantly with the symptoms score or with changes in the levels of IL-5 protein with IL-5 mRNA. These data show that changes in IL-5 mRNA in patients with allergic rhinitis undergoing an allergen challenge correlate with total symptom scores better than changes in IL-5 protein eluted from filter paper. Furthermore, these changes can be measured quantitatively in very small amounts of tissue.

Adult↗
PubMedDate not supplied

Mast cell inhibitor R112 is well tolerated and affects prostaglandin D2 but not other mediators, symptoms, or nasal volumes in a nasal challenge model of allergic rhinitis.

Understanding of the role played by mast cells in allergic rhinitis (AR) has led to the development of novel therapies. The aim of this study was to determine the safety and tolerability of R112, an inhibitor of the tyrosine kinase Syk, in an allergen challenge model of AR. We also examined the effects of R112 on symptoms, mediator release, and nasal airway volumes. This double-blinded, randomized, placebo-controlled, crossover trial enrolled 20 out-of-season volunteers with AR. One intranasal dose of R112 or vehicle was administered and followed by an allergen challenge. In addition to safety monitoring, symptoms; changes in histamine, tryptase, and prostaglandin D2 (PGD2) content of nasal secretions; and acoustic rhinometry were determined over a 15-minute period. R112 was well tolerated. Adverse events were similar between treatments. Five minutes after allergen instillation, PGD2 was decreased when subjects received R112 compared with vehicle (93.4 +/- 23.0 pg/mL versus 171.6 +/- 23.0 pg/mL; p = 0.03), and this correlated with rhinorrhea (p = 0.05). However, at 10 minutes, changes in PGD2, tryptase, and histamine were not significant (46.8 +/- 9.2 pg/mL versus 68.6 +/- 9.2 pg/mL, p = 0.1; 9.5 +/- 2.7 ng/mL versus 16.6 +/- 2.9 ng/mL, p = 0.09; and 1.5 +/- 1.6 ng/mL versus 3.5 +/- 1.6 ng/mL, p = 0.4). No differences were found in symptoms or in acoustic rhinometry between treatment groups. Single-dose R112 appears safe and significantly reduces PGD2 but not histamine or tryptase release in response to allergen challenge in subjects with AR.

Adult↗