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The Anti-Asthma Chinese Herbal Formula ASHMI Provides More Persistent Benefits than Dexamethasone in a Murine Asthma Model
Abstracts AB261
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Impact Of The Intestinal Microbiome On Severe Paramyxoviral Respiratory Infection L. E. Camarda, S. J. Ehlenbach, M. A. Hayward, N. H. Salzman, M. H. Grayson; Medical College of Wisconsin, Milwaukee, WI. RATIONALE: Recent studies have shown that the commensal bacterial species in the intestinal tract (the intestinal microbiome) have the ability to alter the intestinal immune system. It is not known whether the intestinal microbiome can influence immune responses at other mucosal sites. We undertook this study to see whether experimental manipulation of the intestinal microbiome could affect the immune response to severe paramyxoviral infection in the lung. METHODS: C57BL6/J mice from Jackson Laboratories received reverse osmosis (RO) water or RO water supplemented with a non-absorbable antibiotic (streptomycin 0.5 g/250 mLs water) for various amounts of time. The mice were then inoculated intranasally with 23105 pfu/ml Fushimi strain Sendai virus, a viral load that is non-lethal in wild-type mice, and mortality measured. RESULTS: 100% of mice receiving RO water survived the viral infection (n 526). When streptomycin was added to the water prior to and during the viral infection, only 25% of the mice survived (n516). Most mice died between days 9 and 11 post-viral inoculation. When streptomycin was given for 2 weeks followed by switching to RO water at the time of viral inoculation, a similar level of survival (20%, n55) was seen. Survival was not reduced (80%) when streptomycin was given for 1 week followed by RO water for 1 week before viral inoculation (n55). CONCLUSIONS: Disruption of the normal intestinal microbiome leads to significantly increased mortality to a normally non-lethal dose of Sendai virus. Further studies are underway to elucidate the mechanisms that link the intestinal biome with the respiratory immune response.
1012
Effects of Curcumin on LPS-induced Nitric Oxide Production from Murine Macrophages and PBMC of Humans with Respiratory Allergic Disease M. Kim, M. Nowakowski, R. Joks; Center for Asthma & Allergy Research, SUNY Downstate Medical Center, Brooklyn, NY. RATIONALE: Curcumin(Cur), found in curry, is a dietary pigment giving curry its unique color and has anti-inflammatory properties. Airway macrophages of asthmatics are a source of exhaled nitric oxide(NO), which is elevated in active asthma. We determined if Cur suppressed NO production from both a murine macrophage cell line (RAW264.7) and PBMC from allergic asthmatic adult humans(AAAH). METHODS: RAW264.7 cells were stimulated 6 LPS (100 ng/ml) and 6 Cur (1.4-5.4uM). Cur was also added to cells at 1 and 4 days before and after LPS activation to determine time course of suppression. PBMC from AAAH (n54) 6 LPS or allergen were treated 6 Cur. NO2-, a measure of NO, was measured by Greiss reagent on days 3-6. RESULTS: Baseline LPS stimulated NO production from RAW264.7 cells(22.8uM) and was suppressed 73% with maximal Cur concentration (6.2uM); suppression was observed without LPS but not dose-dependently. Cur induced suppression was still present 1 and 4 days after LPS (60% and 9% respectively). NO levels were variable when Cur was added 1 day before LPS and not suppressed when Cur added 4 days before. (p<0.05) PBMC of AAAH produced variable amounts of NO (0.44-7uM) which were not increased with allergen/LPS(2.0-5.85uM) nor suppressed by Cur (2.0-7.42uM) (p50.9). CONCLUSIONS: Cur suppresses LPS-induced NO production in RAW264.7 macrophages in a dose-dependent manner. Neither LPS or allergen stimulated NO production from PBMC of AAAH so evaluation of NO suppressive capacity of Cur was not optimal. The antioxidant activity of Cur on NO production by airway macrophages in asthma needs further investigation.
1013
Influence of Orally Taken Vitamin C on Histamine Levels and Motion Sickness R. Jarisch1, D. Weyer2, E. Ehlert2, C. Koch3, E. Pinkowski4, P. Jung1, W. K€ahler2, R. Girgensohn5, W. Hemmer1, A. Koch2; 1Floridsdorf Allergy Center, Vienna, AUSTRIA, 2Schifffahrtmedizinisches Institut der Marine, Kronshagen, GERMANY, 3Havariekommando, Cuxhaven, GERMANY, 4 Schiffsarzt, Pohlheim, GERMANY, 5SanAmt der Bundeswehr, M€unchen, GERMANY. RATIONALE: Motion sickness is a risk for health and safety for the crew and the ship. Antihistamines are the drug of choice. There is an inverse relation between histamine and vitamin C. We investigated the influence of orally taken vitamin C on the prevention of motion sickness. METHODS: In a double blind placebo controlled cross over study 70 volunteers were exposed to waves in a big indoor swimming pool being in an inflatable life-raft for 20 minutes. One hour before exposure 2g vitamin C or placebo tablets were taken. Before and after exposure blood was taken for determination of histamine, diamine oxidase, tryptase and vitamin C levels. Symptom scores were noted on a visual analogue scale and test persons were asked after the second day which day they felt better. RESULTS: Vitamin C levels increased p< 0.0001, histamine levels increased in all test persons p< 0.001, DAO levels increased in vitamin C persons p<0.0002. Seven persons remained symptom free and were excluded. Results of the visual analogue (n.s.). Test persons felt better taking vitamin C (p< 0.01). There was a significant difference in the state of health between day 1 and 2, despite the drug taken (p<0.01) Out of 63 persons 23 wanted to leave the raft earlier than the demanded 20 minutes: 17 had taken placebo and 6 vitamin C (p<0.03). Male persons felt better with vitamin C (n.s.) and females felt better with vitamin C (p<0.05). CONCLUSIONS: Vitamin C helps to suppress symptoms of motion sickness. Histamine increases being exposed to waves.
1014
The Anti-Asthma Chinese Herbal Formula ASHMI Provides More Persistent Benefits than Dexamethasone in a Murine Asthma Model K. D. Srivastava, H. A. Sampson, X. Li; Pediatric Allergy & Immunology, The Mount Sinai School of Medicine, New York, NY. RATIONALE: Anti-asthma simplified herbal medicine intervention (ASHMI) is a Chinese herbal formula shown to be efficacious in mice and humans. We sought to compare the persistent benefits of ASHMI therapy to steroid treatment using a murine model of asthma. METHODS: Balb/c mice with established asthma induced by ovalbumin (OVA) sensitization and challenges were treated for six weeks with ASHMI, Dexamethasone (Dex), or water (Sham), and then challenged with OVA immediately, 4 and 8 wks post-therapy. Pulmonary and immunological responses were determined following post-therapy challenges. RESULTS: Immediately post-therapy, ASHMI- and Dex-treated mice exhibited similarly reduced airway inflammation, Th2 cytokines and OVAspecific IgE levels compared to sham-treated mice (P<0.05-P<0.001 vs. Sham for both). Brochoalveolar lavage fluid (BALF) from ASHMI but not Dex-treated mice contained elevated Interferon-g (P<0.001 vs. Sham; P<0.001 vs. Dex). Serum corticosterone was reduced in Dex but not ASHMI-treated mice (P<0.05 vs. ASHMI). At 8 weeks post-therapy, ASHMI- but not Dex- treated mice still showed suppression of airway inflammation (P<0.01-P<0.05 vs. Sham; P<0.05- P50.08 vs. Dex) and BALF IL-13 and serum OVA-specific IgE (P<0.001-P<0.05 vs. Sham; P<0.001-P<0.05 vs. Dex). Additionally, ASHMI but not Dex-treated mice exhibited decreased airway hyperreactivity (P<0.001 vs. Sham; P<0.01 vs. Dex). IFN-g levels remained elevated in ASHMI-treated mice (P<0.001 vs. Sham; P<0.001 vs. Dex). CONCLUSIONS: ASHMI therapy provided more persistent benefits than Dex in a murine asthma model, and unlike Dex, was not associated with suppression of INF-g production or reduced adrenal function. ASHMI may be preferable to steroid for asthma therapy. Further clinical study is warranted.
TUESDAY
1011
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Impact Of The Intestinal Microbiome On Severe Paramyxoviral Respiratory Infection L. E. Camarda, S. J. Ehlenbach, M. A. Hayward, N. H. Salzman, M. H. Grayson; Medical College of Wisconsin, Milwaukee, WI. RATIONALE: Recent studies have shown that the commensal bacterial species in the intestinal tract (the intestinal microbiome) have the ability to alter the intestinal immune system. It is not known whether the intestinal microbiome can influence immune responses at other mucosal sites. We undertook this study to see whether experimental manipulation of the intestinal microbiome could affect the immune response to severe paramyxoviral infection in the lung. METHODS: C57BL6/J mice from Jackson Laboratories received reverse osmosis (RO) water or RO water supplemented with a non-absorbable antibiotic (streptomycin 0.5 g/250 mLs water) for various amounts of time. The mice were then inoculated intranasally with 23105 pfu/ml Fushimi strain Sendai virus, a viral load that is non-lethal in wild-type mice, and mortality measured. RESULTS: 100% of mice receiving RO water survived the viral infection (n 526). When streptomycin was added to the water prior to and during the viral infection, only 25% of the mice survived (n516). Most mice died between days 9 and 11 post-viral inoculation. When streptomycin was given for 2 weeks followed by switching to RO water at the time of viral inoculation, a similar level of survival (20%, n55) was seen. Survival was not reduced (80%) when streptomycin was given for 1 week followed by RO water for 1 week before viral inoculation (n55). CONCLUSIONS: Disruption of the normal intestinal microbiome leads to significantly increased mortality to a normally non-lethal dose of Sendai virus. Further studies are underway to elucidate the mechanisms that link the intestinal biome with the respiratory immune response.
1012
Effects of Curcumin on LPS-induced Nitric Oxide Production from Murine Macrophages and PBMC of Humans with Respiratory Allergic Disease M. Kim, M. Nowakowski, R. Joks; Center for Asthma & Allergy Research, SUNY Downstate Medical Center, Brooklyn, NY. RATIONALE: Curcumin(Cur), found in curry, is a dietary pigment giving curry its unique color and has anti-inflammatory properties. Airway macrophages of asthmatics are a source of exhaled nitric oxide(NO), which is elevated in active asthma. We determined if Cur suppressed NO production from both a murine macrophage cell line (RAW264.7) and PBMC from allergic asthmatic adult humans(AAAH). METHODS: RAW264.7 cells were stimulated 6 LPS (100 ng/ml) and 6 Cur (1.4-5.4uM). Cur was also added to cells at 1 and 4 days before and after LPS activation to determine time course of suppression. PBMC from AAAH (n54) 6 LPS or allergen were treated 6 Cur. NO2-, a measure of NO, was measured by Greiss reagent on days 3-6. RESULTS: Baseline LPS stimulated NO production from RAW264.7 cells(22.8uM) and was suppressed 73% with maximal Cur concentration (6.2uM); suppression was observed without LPS but not dose-dependently. Cur induced suppression was still present 1 and 4 days after LPS (60% and 9% respectively). NO levels were variable when Cur was added 1 day before LPS and not suppressed when Cur added 4 days before. (p<0.05) PBMC of AAAH produced variable amounts of NO (0.44-7uM) which were not increased with allergen/LPS(2.0-5.85uM) nor suppressed by Cur (2.0-7.42uM) (p50.9). CONCLUSIONS: Cur suppresses LPS-induced NO production in RAW264.7 macrophages in a dose-dependent manner. Neither LPS or allergen stimulated NO production from PBMC of AAAH so evaluation of NO suppressive capacity of Cur was not optimal. The antioxidant activity of Cur on NO production by airway macrophages in asthma needs further investigation.
1013
Influence of Orally Taken Vitamin C on Histamine Levels and Motion Sickness R. Jarisch1, D. Weyer2, E. Ehlert2, C. Koch3, E. Pinkowski4, P. Jung1, W. K€ahler2, R. Girgensohn5, W. Hemmer1, A. Koch2; 1Floridsdorf Allergy Center, Vienna, AUSTRIA, 2Schifffahrtmedizinisches Institut der Marine, Kronshagen, GERMANY, 3Havariekommando, Cuxhaven, GERMANY, 4 Schiffsarzt, Pohlheim, GERMANY, 5SanAmt der Bundeswehr, M€unchen, GERMANY. RATIONALE: Motion sickness is a risk for health and safety for the crew and the ship. Antihistamines are the drug of choice. There is an inverse relation between histamine and vitamin C. We investigated the influence of orally taken vitamin C on the prevention of motion sickness. METHODS: In a double blind placebo controlled cross over study 70 volunteers were exposed to waves in a big indoor swimming pool being in an inflatable life-raft for 20 minutes. One hour before exposure 2g vitamin C or placebo tablets were taken. Before and after exposure blood was taken for determination of histamine, diamine oxidase, tryptase and vitamin C levels. Symptom scores were noted on a visual analogue scale and test persons were asked after the second day which day they felt better. RESULTS: Vitamin C levels increased p< 0.0001, histamine levels increased in all test persons p< 0.001, DAO levels increased in vitamin C persons p<0.0002. Seven persons remained symptom free and were excluded. Results of the visual analogue (n.s.). Test persons felt better taking vitamin C (p< 0.01). There was a significant difference in the state of health between day 1 and 2, despite the drug taken (p<0.01) Out of 63 persons 23 wanted to leave the raft earlier than the demanded 20 minutes: 17 had taken placebo and 6 vitamin C (p<0.03). Male persons felt better with vitamin C (n.s.) and females felt better with vitamin C (p<0.05). CONCLUSIONS: Vitamin C helps to suppress symptoms of motion sickness. Histamine increases being exposed to waves.
1014
The Anti-Asthma Chinese Herbal Formula ASHMI Provides More Persistent Benefits than Dexamethasone in a Murine Asthma Model K. D. Srivastava, H. A. Sampson, X. Li; Pediatric Allergy & Immunology, The Mount Sinai School of Medicine, New York, NY. RATIONALE: Anti-asthma simplified herbal medicine intervention (ASHMI) is a Chinese herbal formula shown to be efficacious in mice and humans. We sought to compare the persistent benefits of ASHMI therapy to steroid treatment using a murine model of asthma. METHODS: Balb/c mice with established asthma induced by ovalbumin (OVA) sensitization and challenges were treated for six weeks with ASHMI, Dexamethasone (Dex), or water (Sham), and then challenged with OVA immediately, 4 and 8 wks post-therapy. Pulmonary and immunological responses were determined following post-therapy challenges. RESULTS: Immediately post-therapy, ASHMI- and Dex-treated mice exhibited similarly reduced airway inflammation, Th2 cytokines and OVAspecific IgE levels compared to sham-treated mice (P<0.05-P<0.001 vs. Sham for both). Brochoalveolar lavage fluid (BALF) from ASHMI but not Dex-treated mice contained elevated Interferon-g (P<0.001 vs. Sham; P<0.001 vs. Dex). Serum corticosterone was reduced in Dex but not ASHMI-treated mice (P<0.05 vs. ASHMI). At 8 weeks post-therapy, ASHMI- but not Dex- treated mice still showed suppression of airway inflammation (P<0.01-P<0.05 vs. Sham; P<0.05- P50.08 vs. Dex) and BALF IL-13 and serum OVA-specific IgE (P<0.001-P<0.05 vs. Sham; P<0.001-P<0.05 vs. Dex). Additionally, ASHMI but not Dex-treated mice exhibited decreased airway hyperreactivity (P<0.001 vs. Sham; P<0.01 vs. Dex). IFN-g levels remained elevated in ASHMI-treated mice (P<0.001 vs. Sham; P<0.001 vs. Dex). CONCLUSIONS: ASHMI therapy provided more persistent benefits than Dex in a murine asthma model, and unlike Dex, was not associated with suppression of INF-g production or reduced adrenal function. ASHMI may be preferable to steroid for asthma therapy. Further clinical study is warranted.
TUESDAY
1011