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Determination of mRNA Expression and Serum Levels for IL-4 and IL-13 in Asmathic Patients
S140 Abstracts
550
SUNDAY
Determination of mRNA Expression and Serum Levels for IL-4 and IL-13 in Asmathic Patients R. Farid, J. Tavakol Afshari, M. Boskabadi; Mashad University Medical Sciences, Mashad, IRAN (ISLAMIC REPUBLIC OF). INTORDUCTION: Immune and inflammatory responses that mediated by cytokines play an important relo in the pathophisiology of asthma. These responses are associated with over expression of Th2 cytokines such as IL-4 and IL13. These two sytokines use shared receptors for signaling that lead to identical immunological effects and the requlation of the Th1/Th2 balance. The aim of this study was to determine whether patients during asthmatic attack had over-expression of IL-4 and IL-13 genes. MATERIALS AND METHODS: Using RT-PCR, we examined IL4 and IL-13 mRNA gene expression in twenty asthmatic cases and twenty healty individual who had not symptoms or history of asthma and other allergic disease. Extracted mRNA form activated PBMCs of one healthy control with PHA is used as positive control. Total serum IgE and IL-4 level were determined by ELISA Method. RESULTS: IL-13 mRNA expression in 70% of patients during asthmatic attack increased in resoect to control (p-value50.01) but no correlation exist between IL-13 mRNA and total serum IgE (p-value50.0708). Thirty percent of patients had IL-4 gene expression by RT-PCR(P50.01), but none of controls had IL-4 gene expression. Mean serum IgE level in patients and in normal indiciduals were 84.9 IU/ml and 62.2 IU/ml (p50.01) respectively. Thirty percent of patients had IgE level greater than 100 IU.ml (p50.01). There was correalation between serum IgE and IL-4 in 73% of cases. CONCLUSION AND DISCUSSION: The results showed that, there is some correlation betweem IL-4 gene expression and serum IL-4. All results indicate that serum IgE and IL-4 concentratin is considerably higher in asthmatics than non-asthmatic controls. There is a correlation between IL-4 gene expression and IL-4 glycoprotien in serum as a gene product. IL-13 mRNA expression in 70% of patients during asthmatic attack increased in respect to cintrols. Eventually, this study provides additional evidence that Th2 cytokines (IL-13 , IL-4) gene expression play a key role in the imbalance of Th1/Th2 in asthmatic patients; but the role of IL-13 in more significant. KEY WORDS: Asthma, IL-4, IL-13, RT-PCR. Funding: Bu-Ali Research Center
551
Prevalence of Nonallergic Triggers among Seasonal Allergic Rhinitics and Normals D. Shusterman1, M. Murphy2; 1University of Washington, Seattle, WA, 2 University of California, San Francisco, CA. RATIONALE: Nonallergic rhinitis is defined by hyperreactivity to physical and chemical stimuli. Typical triggers include cold-dry air, cleaning products, fragrances, tobacco smoke, exercise, alcohol, spicy foods, and bright lights. Allergic rhinitics may also react to nonallergic triggers. We examined the reporting of specific nonallergic nasal symptom triggers in seasonal allergic rhinitics, comparing them with non-rhinitics in a structured sample of subjects. METHODS: Sixty subjects were recruited for a study of chemosensory function, stratified by age, gender, and allergic rhinitis status. Subjects ranged in age from 19 to 68 years, and were counter-balanced with respect to gender and skin test reactivity. In a sub-questionnaire, subjects were queried with regard to self-reported nonallergic nasal symptom triggers on a scale of 0-8. RESULTS: Across all subjects, nonallergic rhinitis scores were bimodal, with peaks at 1 and 5. However, the majority highly reactive subjects (>3 triggers) were allergic rhinitics, with 42% of allergic rhinitic subjects reporting >3 triggers, compared with only 3% of controls (p < 0.01). Subjects over age 35 were more likely to report one or more nonallergic triggers, particularly tobacco smoke (p<0.05). Gender did not predict overall score or specific symptom triggers. Only one trigger-hot/spicy foodswas equally prevalent in the two subgroups.
J ALLERGY CLIN IMMUNOL JANUARY 2007
CONCLUSIONS: Allergic rhinitics, on average, reported more nonallergic symptom triggers than did nonrhinitics, and subjects over age 35 were more likely to report at least one symptom trigger. Hyperreactivity to nonallergic stimuli is a phenotypic trait shared by nonallergic rhinitics and a substantial fraction of allergic rhinitics as well. Funding: NIH
552
Role Of Prostaglandin D2 And E2 Terminal Synthases In Chronic Rhinosinusitis M. Okano1, T. Fujiwara1, M. Yamamoto1, H. Hattori1, K. Nishizaki1, Y. Sugata1, Y. Urade2; 1Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JAPAN, 2Osaka Bioscience Institute, Osaka, JAPAN. RATIONALE: We sought to determine the role of prostaglandin D2 synthese (PGDS) and prostaglandin E2 synthase (PGES) in the pathophysiology of chronic rhinosinusitis (CRS). METHODS: The study examined the expression of PGDS and PGES in nasal polyps of 22 CRS patients. As controls, uncinate process mucosae were obtained from 12 CRS patients not having nasal polyps and 5 subjects without sinusitis. Immunohistochemistry and quantitative real-time PCR were used to evaluate the expression. RESULTS: Both PGDS and PGES were detected in nasal polyps by immunohistochemistry. Significantly greater levels of PGDS mRNA and lesser levels of PGES mRNA were observed in the nasal polyps as compared with uncinate process mucosae, and an inverse correlation between PGDS and PGES expression was observed. Levels of PGDS mRNA in nasal polyps were positively correlated with degree of infiltration by EG21 eosinophils, whereas the levels of PGES were inversely correlated. Significantly increased levels of PGDS and conversely decreased levels of PGES were observed in asthmatics as compared with non-asthmatics. In addition, PGDS and PGES levels were positively and inversely correlated with the radiological severity of sinusitis, respectively. CONCLUSIONS: These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation. Funding: Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (no. 14704043), as well as a grant in aid of Research on Allergic disease and Immunology from the Ministry of Health, Labor and Welfare (no. 14210301)
553
Cytokines and Chemokines in NARES and Nasal Polyposis C. Klemens1, F. Jund1, A. Klemens2, C. Devens1, M. F. 1 1 Kramer ; Oto-Rhino-Laryngology, Head and Neck Surgery, LudwigMaximilians-University Munich, Munich, GERMANY, 2Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Zentralklinikum Augsburg, Augsburg, GERMANY. RATIONALE: NARES (non-allergic rhinitis with eosinophilia syndrome) and non-allergic nasal polyposis (NP) both constitute chronic forms of nasal inflammation, which are characterized by eosinophilia. The objective of the study was to look for similarities and differences in the nasal cytokine patterns of the two diseases. METHODS: Nasal secretions of 31 patients suffering from NARES, 16 non-atopic patients with nasal polyposis and 20 healthy controls were gained by the cotton wool method and analyzed for IL-1b, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, IFN-g, TNF-a, MCP-1, and MIP1b (Bio-Plex Cytokine Assay). RESULTS: We found high and significantly elevated levels of pro- inflammatory cytokines IL-1b, IL-6, IFN-g and TNF-a in nasal secretions of patients with NARES compared to healthy controls and NP. IL-4 and IL-5 showed high levels in NARES, while in NP IL-5 and IL-13 showed the highest concentrations. G-CSF and IL-8 were highest in NP samples, while MCP-1 and MIP-1b showed likewise elevated levels in NARES and NP. CONCLUSIONS: The high levels of pro-inflammatory cytokines in NARES are an indicator for the chronic, self-perpetuating process of
550
SUNDAY
Determination of mRNA Expression and Serum Levels for IL-4 and IL-13 in Asmathic Patients R. Farid, J. Tavakol Afshari, M. Boskabadi; Mashad University Medical Sciences, Mashad, IRAN (ISLAMIC REPUBLIC OF). INTORDUCTION: Immune and inflammatory responses that mediated by cytokines play an important relo in the pathophisiology of asthma. These responses are associated with over expression of Th2 cytokines such as IL-4 and IL13. These two sytokines use shared receptors for signaling that lead to identical immunological effects and the requlation of the Th1/Th2 balance. The aim of this study was to determine whether patients during asthmatic attack had over-expression of IL-4 and IL-13 genes. MATERIALS AND METHODS: Using RT-PCR, we examined IL4 and IL-13 mRNA gene expression in twenty asthmatic cases and twenty healty individual who had not symptoms or history of asthma and other allergic disease. Extracted mRNA form activated PBMCs of one healthy control with PHA is used as positive control. Total serum IgE and IL-4 level were determined by ELISA Method. RESULTS: IL-13 mRNA expression in 70% of patients during asthmatic attack increased in resoect to control (p-value50.01) but no correlation exist between IL-13 mRNA and total serum IgE (p-value50.0708). Thirty percent of patients had IL-4 gene expression by RT-PCR(P50.01), but none of controls had IL-4 gene expression. Mean serum IgE level in patients and in normal indiciduals were 84.9 IU/ml and 62.2 IU/ml (p50.01) respectively. Thirty percent of patients had IgE level greater than 100 IU.ml (p50.01). There was correalation between serum IgE and IL-4 in 73% of cases. CONCLUSION AND DISCUSSION: The results showed that, there is some correlation betweem IL-4 gene expression and serum IL-4. All results indicate that serum IgE and IL-4 concentratin is considerably higher in asthmatics than non-asthmatic controls. There is a correlation between IL-4 gene expression and IL-4 glycoprotien in serum as a gene product. IL-13 mRNA expression in 70% of patients during asthmatic attack increased in respect to cintrols. Eventually, this study provides additional evidence that Th2 cytokines (IL-13 , IL-4) gene expression play a key role in the imbalance of Th1/Th2 in asthmatic patients; but the role of IL-13 in more significant. KEY WORDS: Asthma, IL-4, IL-13, RT-PCR. Funding: Bu-Ali Research Center
551
Prevalence of Nonallergic Triggers among Seasonal Allergic Rhinitics and Normals D. Shusterman1, M. Murphy2; 1University of Washington, Seattle, WA, 2 University of California, San Francisco, CA. RATIONALE: Nonallergic rhinitis is defined by hyperreactivity to physical and chemical stimuli. Typical triggers include cold-dry air, cleaning products, fragrances, tobacco smoke, exercise, alcohol, spicy foods, and bright lights. Allergic rhinitics may also react to nonallergic triggers. We examined the reporting of specific nonallergic nasal symptom triggers in seasonal allergic rhinitics, comparing them with non-rhinitics in a structured sample of subjects. METHODS: Sixty subjects were recruited for a study of chemosensory function, stratified by age, gender, and allergic rhinitis status. Subjects ranged in age from 19 to 68 years, and were counter-balanced with respect to gender and skin test reactivity. In a sub-questionnaire, subjects were queried with regard to self-reported nonallergic nasal symptom triggers on a scale of 0-8. RESULTS: Across all subjects, nonallergic rhinitis scores were bimodal, with peaks at 1 and 5. However, the majority highly reactive subjects (>3 triggers) were allergic rhinitics, with 42% of allergic rhinitic subjects reporting >3 triggers, compared with only 3% of controls (p < 0.01). Subjects over age 35 were more likely to report one or more nonallergic triggers, particularly tobacco smoke (p<0.05). Gender did not predict overall score or specific symptom triggers. Only one trigger-hot/spicy foodswas equally prevalent in the two subgroups.
J ALLERGY CLIN IMMUNOL JANUARY 2007
CONCLUSIONS: Allergic rhinitics, on average, reported more nonallergic symptom triggers than did nonrhinitics, and subjects over age 35 were more likely to report at least one symptom trigger. Hyperreactivity to nonallergic stimuli is a phenotypic trait shared by nonallergic rhinitics and a substantial fraction of allergic rhinitics as well. Funding: NIH
552
Role Of Prostaglandin D2 And E2 Terminal Synthases In Chronic Rhinosinusitis M. Okano1, T. Fujiwara1, M. Yamamoto1, H. Hattori1, K. Nishizaki1, Y. Sugata1, Y. Urade2; 1Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JAPAN, 2Osaka Bioscience Institute, Osaka, JAPAN. RATIONALE: We sought to determine the role of prostaglandin D2 synthese (PGDS) and prostaglandin E2 synthase (PGES) in the pathophysiology of chronic rhinosinusitis (CRS). METHODS: The study examined the expression of PGDS and PGES in nasal polyps of 22 CRS patients. As controls, uncinate process mucosae were obtained from 12 CRS patients not having nasal polyps and 5 subjects without sinusitis. Immunohistochemistry and quantitative real-time PCR were used to evaluate the expression. RESULTS: Both PGDS and PGES were detected in nasal polyps by immunohistochemistry. Significantly greater levels of PGDS mRNA and lesser levels of PGES mRNA were observed in the nasal polyps as compared with uncinate process mucosae, and an inverse correlation between PGDS and PGES expression was observed. Levels of PGDS mRNA in nasal polyps were positively correlated with degree of infiltration by EG21 eosinophils, whereas the levels of PGES were inversely correlated. Significantly increased levels of PGDS and conversely decreased levels of PGES were observed in asthmatics as compared with non-asthmatics. In addition, PGDS and PGES levels were positively and inversely correlated with the radiological severity of sinusitis, respectively. CONCLUSIONS: These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation. Funding: Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (no. 14704043), as well as a grant in aid of Research on Allergic disease and Immunology from the Ministry of Health, Labor and Welfare (no. 14210301)
553
Cytokines and Chemokines in NARES and Nasal Polyposis C. Klemens1, F. Jund1, A. Klemens2, C. Devens1, M. F. 1 1 Kramer ; Oto-Rhino-Laryngology, Head and Neck Surgery, LudwigMaximilians-University Munich, Munich, GERMANY, 2Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Zentralklinikum Augsburg, Augsburg, GERMANY. RATIONALE: NARES (non-allergic rhinitis with eosinophilia syndrome) and non-allergic nasal polyposis (NP) both constitute chronic forms of nasal inflammation, which are characterized by eosinophilia. The objective of the study was to look for similarities and differences in the nasal cytokine patterns of the two diseases. METHODS: Nasal secretions of 31 patients suffering from NARES, 16 non-atopic patients with nasal polyposis and 20 healthy controls were gained by the cotton wool method and analyzed for IL-1b, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, IFN-g, TNF-a, MCP-1, and MIP1b (Bio-Plex Cytokine Assay). RESULTS: We found high and significantly elevated levels of pro- inflammatory cytokines IL-1b, IL-6, IFN-g and TNF-a in nasal secretions of patients with NARES compared to healthy controls and NP. IL-4 and IL-5 showed high levels in NARES, while in NP IL-5 and IL-13 showed the highest concentrations. G-CSF and IL-8 were highest in NP samples, while MCP-1 and MIP-1b showed likewise elevated levels in NARES and NP. CONCLUSIONS: The high levels of pro-inflammatory cytokines in NARES are an indicator for the chronic, self-perpetuating process of