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A Surveillance Study of Natural Rhinovirus Colds in Young Adults with Mild Asthma
S56 Abstracts
SATURDAY
200
Th2 Cytokines Potently Induce the Expression of an Orexigenic Peptide, Melanin-Concentrating Hormone by Human Vascular Endothelial Cells H. Morita1,2, K. Orihara1, A. Yagami1,3, R. Kojima1, K. Matsumoto1, H. Saito1, A. Matsuda1; 1National Research Institute for Child Health and Development, Tokyo, Japan, 2Department of Pediatrics, School of Medicine, Keio University, Tokyo, Japan, 3Department of Dermatology, Fujita Health University School of Medicine, Aichi, Japan. RATIONALE: Melanin-concentrating hormone (MCH) is expressed predominantly in neurons of the lateral hypothalamus and is an important regulator of energy homeostasis and food intake. However, little is known about the physiological relevance and major source of MCH in the peripheral. Preliminary, we have developed a gene expression profile of human microvascular endothelial cells from normal lung blood vessels (HMVEC-LBl) stimulated with IL-4, and found that pro-MCH (PMCH), which encodes MCH was the most highly upregulated gene in response to IL-4. METHODS: We examined the cytokine induced expression of PMCH by real-time PCR in HMVEC-LBl, and in other human primary airway structural cells, as well as in other human primary endothelial cells. The concentration of MCH in the culture supernatant was measured by ELISA. STAT6 mRNA expression in HMVEC-LBl was inhibited by specific small interference RNA. RESULTS: IL-13, as well as IL-4 was found to potently induce the mRNA expression of PMCH. The IL-4-induced expression of PMCH mRNA was also observed in other endothelial cells, but not in other airway structural cells. The accumulation of MCH peptides was also found to be induced by IL-4 treatment specifically in the vascular endothelial cells. We also revealed that STAT6 is required for IL-4-induced expression of PMCH. CONCLUSIONS: These results demonstrated that the orexigenic peptide, MCH, is produced by Th2 cytokine-stimulated human vascular endothelial cells and may provide a mechanistic link between allergic inflammation, asthma and obesity. FUNDINGS: National Institute of Biomedical Innovation (ID05-24)
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Curcumin Attenuates Airway Hyperresponsiveness and Inflammation in Murine Asthma Model J. Lee1, J. Jeung1, M. Oh2, B. Lee1, D. Choi1; 1Samsung medical center, Seoul, Republic of Korea, 2Bundang Jesaeng Hospital, Seongnam, Republic of Korea. RATIONALE: Anti-asthmatic property of curcumin, a natural product from the rhizomes of Curcuma longa, has been tested in a murine acute asthma model. METHODS: Six week-old female BALB/c mice were sensitized and exposed to aerosolized ovalbumin (OVA). Methacholine bronchoprovocation test and bronchoalveolar lavage (BAL) fluid analyses were performed. BALB/c mice were treated with indicated dose of curcumin for four times (25 mg/kg, 50 mg/kg, each n 5 5) 24 hr before allergen challenge. RESULTS: Airway inflammation was decreased in curcumin treated groups compared with positive control group. Total cell counts (positive control 463 x103/ml, high dose curcumin group 215 x103/ml, p 5 0.014) and eosinophil counts (positive control 284 x103/ml, high dose curcumin group 126 x103/ml, p 5 0.003) were decreased after curcumin administration. Only high dose Curcumin inhibited OVA-induced airway hyperreactivity (positive control PC200 5 4.04 mg/ml, high dose curcumin group PC200 5 6.72, p 5 0.033). CONCLUSIONS: The results demonstrated that curcumin is effective in improving the airways inflammations in the OVA-sensitized BALB/c mice. The possible anti-asthmatic mechanism of curcumin should be elucidated.
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
202
The Critical Role of Histamine H4 Receptor in the Development of Allergic Rhinitis in Mice Y. Shiraishi1, K. Takeda1, R. L. Thurmond2, E. W. Gelfand1; 1National Jewish Health, Denver, CO, 2Johnson & Johnson Pharmaceutical Research & Development, San Diego, CA. RATIONALE: Histamine is one of the most important inflammatory mediators in allergic upper airway diseases including allergic rhinitis. Recently, the histamine H4 receptor (H4R) was discovered, but the role of this receptor in the pathogenesis of allergic rhinitis has not been defined. We examined H4R function in the early- and late-phase responses of allergic rhinitis in mice. METHODS: Wild-type (WT) mice and H4R-deficient (H4R-/-) mice were sensitized to OVA by intraperitoneal injection and then challenged intranasally with OVA or saline without anesthesia on 6 consecutive days. Respiratory frequency (RF) was monitored by whole body plethysmography at 3 different time points: prior to the first OVA challenge as baseline, just after the 4th OVA challenge in the early-phase response (EPR), and 24 hrs after the 6th OVA challenge in the late-phase response (LPR). Nasal resistance (RNA) was measured 24 hrs after the 6th OVA challenge. RESULTS: In the EPR, WT mice showed a significant decrease in RF after the 4th OVA challenge; however, H4R-/- mice showed no change in RF compared to baseline, suggesting the absence of an EPR. In the LPR, decreases in RF and increases in RNA were observed in WT mice but not in the H4R-/- mice. CONCLUSIONS: We conclude that H4R may play a critical role in the development of both the early and late-phase responses in allergic rhinitis.
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A Surveillance Study of Natural Rhinovirus Colds in Young Adults with Mild Asthma A. Stallings, A. McLaughlin, D. Murphy, H. Carper, T. Platts-Mills, P. Heymann; University of Virginia, Charlottesville, VA. RATIONALE: Rhinovirus (RV) infections are strongly associated with asthma exacerbations in children and young adults. The frequency of these infections and host factors which increase the risk for lower airway symptoms induced by RV needs further study. METHODS: Sixteen subjects, (ages 18-39), with a history of mild allergic asthma and positive methacholine challenges were enrolled. Upper and lower airway symptom scores, peak expiratory flow (PEF) tests and FEV1’s were monitored daily at home. Spirometry was performed and nasal washes were obtained to test for RV by RT-PCR every two weeks. Subjects were also asked to come to clinic within 48 hours of acute cold symptoms or a decline in FEV1 by > 20%. Subjects were randomized to receive omalizumab or placebo subcutaneously during the three months of surveillance. RESULTS: Among 16 subjects (total IgE 221-560 IU/mL), 10 were positive for RV during at least one clinic visit. Four subjects tested positive at two separate clinic visits. There were no significant changes in PEF or FEV1 associated with positive tests for RV. Five subjects came into the clinic for acute symptoms, and only one of these visits was associated with a positive test for RV. Five of 14 positive tests for RVoccurred in subjects receiving placebo. Of the 9 positive tests in subjects receiving omalizumab, 4 were positive on the first clinic visit before omalizumab could be effective. CONCLUSIONS: RV infections occurred frequently during this study of mild asthmatic adults, but were not associated with chest symptoms or significant changes in lung function.
SATURDAY
200
Th2 Cytokines Potently Induce the Expression of an Orexigenic Peptide, Melanin-Concentrating Hormone by Human Vascular Endothelial Cells H. Morita1,2, K. Orihara1, A. Yagami1,3, R. Kojima1, K. Matsumoto1, H. Saito1, A. Matsuda1; 1National Research Institute for Child Health and Development, Tokyo, Japan, 2Department of Pediatrics, School of Medicine, Keio University, Tokyo, Japan, 3Department of Dermatology, Fujita Health University School of Medicine, Aichi, Japan. RATIONALE: Melanin-concentrating hormone (MCH) is expressed predominantly in neurons of the lateral hypothalamus and is an important regulator of energy homeostasis and food intake. However, little is known about the physiological relevance and major source of MCH in the peripheral. Preliminary, we have developed a gene expression profile of human microvascular endothelial cells from normal lung blood vessels (HMVEC-LBl) stimulated with IL-4, and found that pro-MCH (PMCH), which encodes MCH was the most highly upregulated gene in response to IL-4. METHODS: We examined the cytokine induced expression of PMCH by real-time PCR in HMVEC-LBl, and in other human primary airway structural cells, as well as in other human primary endothelial cells. The concentration of MCH in the culture supernatant was measured by ELISA. STAT6 mRNA expression in HMVEC-LBl was inhibited by specific small interference RNA. RESULTS: IL-13, as well as IL-4 was found to potently induce the mRNA expression of PMCH. The IL-4-induced expression of PMCH mRNA was also observed in other endothelial cells, but not in other airway structural cells. The accumulation of MCH peptides was also found to be induced by IL-4 treatment specifically in the vascular endothelial cells. We also revealed that STAT6 is required for IL-4-induced expression of PMCH. CONCLUSIONS: These results demonstrated that the orexigenic peptide, MCH, is produced by Th2 cytokine-stimulated human vascular endothelial cells and may provide a mechanistic link between allergic inflammation, asthma and obesity. FUNDINGS: National Institute of Biomedical Innovation (ID05-24)
201
Curcumin Attenuates Airway Hyperresponsiveness and Inflammation in Murine Asthma Model J. Lee1, J. Jeung1, M. Oh2, B. Lee1, D. Choi1; 1Samsung medical center, Seoul, Republic of Korea, 2Bundang Jesaeng Hospital, Seongnam, Republic of Korea. RATIONALE: Anti-asthmatic property of curcumin, a natural product from the rhizomes of Curcuma longa, has been tested in a murine acute asthma model. METHODS: Six week-old female BALB/c mice were sensitized and exposed to aerosolized ovalbumin (OVA). Methacholine bronchoprovocation test and bronchoalveolar lavage (BAL) fluid analyses were performed. BALB/c mice were treated with indicated dose of curcumin for four times (25 mg/kg, 50 mg/kg, each n 5 5) 24 hr before allergen challenge. RESULTS: Airway inflammation was decreased in curcumin treated groups compared with positive control group. Total cell counts (positive control 463 x103/ml, high dose curcumin group 215 x103/ml, p 5 0.014) and eosinophil counts (positive control 284 x103/ml, high dose curcumin group 126 x103/ml, p 5 0.003) were decreased after curcumin administration. Only high dose Curcumin inhibited OVA-induced airway hyperreactivity (positive control PC200 5 4.04 mg/ml, high dose curcumin group PC200 5 6.72, p 5 0.033). CONCLUSIONS: The results demonstrated that curcumin is effective in improving the airways inflammations in the OVA-sensitized BALB/c mice. The possible anti-asthmatic mechanism of curcumin should be elucidated.
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
202
The Critical Role of Histamine H4 Receptor in the Development of Allergic Rhinitis in Mice Y. Shiraishi1, K. Takeda1, R. L. Thurmond2, E. W. Gelfand1; 1National Jewish Health, Denver, CO, 2Johnson & Johnson Pharmaceutical Research & Development, San Diego, CA. RATIONALE: Histamine is one of the most important inflammatory mediators in allergic upper airway diseases including allergic rhinitis. Recently, the histamine H4 receptor (H4R) was discovered, but the role of this receptor in the pathogenesis of allergic rhinitis has not been defined. We examined H4R function in the early- and late-phase responses of allergic rhinitis in mice. METHODS: Wild-type (WT) mice and H4R-deficient (H4R-/-) mice were sensitized to OVA by intraperitoneal injection and then challenged intranasally with OVA or saline without anesthesia on 6 consecutive days. Respiratory frequency (RF) was monitored by whole body plethysmography at 3 different time points: prior to the first OVA challenge as baseline, just after the 4th OVA challenge in the early-phase response (EPR), and 24 hrs after the 6th OVA challenge in the late-phase response (LPR). Nasal resistance (RNA) was measured 24 hrs after the 6th OVA challenge. RESULTS: In the EPR, WT mice showed a significant decrease in RF after the 4th OVA challenge; however, H4R-/- mice showed no change in RF compared to baseline, suggesting the absence of an EPR. In the LPR, decreases in RF and increases in RNA were observed in WT mice but not in the H4R-/- mice. CONCLUSIONS: We conclude that H4R may play a critical role in the development of both the early and late-phase responses in allergic rhinitis.
203
A Surveillance Study of Natural Rhinovirus Colds in Young Adults with Mild Asthma A. Stallings, A. McLaughlin, D. Murphy, H. Carper, T. Platts-Mills, P. Heymann; University of Virginia, Charlottesville, VA. RATIONALE: Rhinovirus (RV) infections are strongly associated with asthma exacerbations in children and young adults. The frequency of these infections and host factors which increase the risk for lower airway symptoms induced by RV needs further study. METHODS: Sixteen subjects, (ages 18-39), with a history of mild allergic asthma and positive methacholine challenges were enrolled. Upper and lower airway symptom scores, peak expiratory flow (PEF) tests and FEV1’s were monitored daily at home. Spirometry was performed and nasal washes were obtained to test for RV by RT-PCR every two weeks. Subjects were also asked to come to clinic within 48 hours of acute cold symptoms or a decline in FEV1 by > 20%. Subjects were randomized to receive omalizumab or placebo subcutaneously during the three months of surveillance. RESULTS: Among 16 subjects (total IgE 221-560 IU/mL), 10 were positive for RV during at least one clinic visit. Four subjects tested positive at two separate clinic visits. There were no significant changes in PEF or FEV1 associated with positive tests for RV. Five subjects came into the clinic for acute symptoms, and only one of these visits was associated with a positive test for RV. Five of 14 positive tests for RVoccurred in subjects receiving placebo. Of the 9 positive tests in subjects receiving omalizumab, 4 were positive on the first clinic visit before omalizumab could be effective. CONCLUSIONS: RV infections occurred frequently during this study of mild asthmatic adults, but were not associated with chest symptoms or significant changes in lung function.