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Inhaled interleukin-10 before and after induction of experimental endotoxemia in the rat [Elektronische Ressource] : effects on the inflammatory response / vorgelegt von Nguyen, Ngoc Thach

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Aus dem Fachbereich Medizin der Johann Wolfgang Goethe-Universität Frankfurt am Main Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie Direktor Prof. Dr.med. Dr.med.habil. Bernhard Zwissler Inhaled Interleukin-10 before and after induction of experimental endotoxemia in the rat. Effects on the inflammatory response. Dissertation zur Erlangung des Doktorgrades der Medizin des Fachbereichs Medizin der Johann Wolfgang Goethe-Universität Frankfurt am Main vorgelegt von Nguyen, Ngoc Thach aus Hanoi, Vietnam Frankfurt am Main, 2007 Dekan : Prof. Dr. J. Pfeilschifter Referent : Prof. Dr. B. Zwißler Koreferent: Priv. - Doz. Dr. H. Mühl Tag der mündlichen Prüfung: 21. August 2007 To my wife Hà Thị Thu Hiền and daughter Nguyễn Hà Quỳnh Anh and to the memories of my father Prof. Nguyễn Hữu Mô and my mother Thạch Thị Lợi. CONTENT Pages Abbreviations 1. Introduction 1 1.1. Definition and Epidemiology of Acute Respiratory Distress Syndrome (ARDS) 1 1.2. Etiology and Pathophysiology of ARDS 1 1.2.1. Etiology of ARDS 1 1.2.2. Pathophysiology of ARDS 2 1.3. Anti-inflammatory Therapy and ARDS 3 1.3.1. Interleukin-10 and ARDS 3 1.4. Objective 5 2. Materials and Methods 6 2.1. Animals 6 2.2. Anaesthesia and Surgical Preparation 6 2.3. Mechanical Ventilation 8 2.4. Nebulisation 8 2.5. Experimental Protocol of the Present Study 11 2.5.1. Preparation of LPS 11 2.5.2.

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Published by
Published 01 January 2007
Reads 39
Language English
Aus dem Fachbereich Medizin
der Johann Wolfgang Goethe-Universität
Frankfurt am Main
Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
Direktor Prof. Dr.med. Dr.med.habil. Bernhard Zwissler
 
Inhaled Interleukin-10 before and after induction of
experimental endotoxemia in the rat.
Effects on the inflammatory response.
 
Dissertation
zur Erlangung des Doktorgrades der Medizin
des Fachbereichs Medizin
der Johann Wolfgang Goethe-Universität Frankfurt am Main
 
vorgelegt von 
Nguyen, Ngoc Thach
 
aus Hanoi, Vietnam
 
Frankfurt am Main, 2007
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dekan : Prof. Dr. J. Pfeilschifter
Referent : Prof. Dr. B. Zwißler
Koreferent: Priv. - Doz. Dr. H. Mühl
 
Tag der mündlichen Prüfung: 21. August 2007
 
 
 
 
 
 
 
 
 
To my wife Hà ThThu Hin and daughter Nguyn Hà Qunh Anh
and to the memories of my father Prof. Nguyn Hu Mô and my mother Thch ThLi.
CONTENT  Abbreviations 1. Introduction 1.1. Definition and Epidemiology of Acute Respiratory Distress Syndrome (ARDS) 1.2. Etiology and Pathophysiology of ARDS 1.2.1. Etiology of ARDS 1.2.2. Pathophysiology of ARDS 1.3. Anti-inflammatory Therapy and ARDS 1.3.1. Interleukin-10 and ARDS 1.4. Objective 2. Materials and Methods 2.1. Animals 2.2. Anaesthesia and Surgical Preparation 2.3. Mechanical Ventilation 2.4. Nebulisation 2.5. Experimental Protocol of the Present Study 2.5.1. Preparation of LPS 2.5.2. Preparation of Interleukin-10 2.5.3. Protocol of Experiments 2.6. Bronchoalveolar Lavage, Isolation, and Culture of Alveolar Macrophages 2.7. Processing of Plasma Samples 2.8. Nitrite Assay 2.9. Enzyme Linked Immunosorbent Assay 2.10. Statistics
Pages  1 1 1 1 2 3 3 5 6 6 6 8 8 11 11 11 11 13 14 14 14 15
3. Results 3.1. Haemodynamics 3.2. Arterial Blood Gas Analysis 3.3. Alveolar Macrophages and Nitrite Release from cultured Alveolar Macrophages 3.4. Cytokine concentrations in BALF 3.5. Cytokine concentrations in Plasma 4. Discussion 4.1. Methods 4.1.1. Aerosol Therapy 4.1.2. Experimental endotoxemia 4.2. Results 4.2.1. Haemodynamics 4.2.2. Arterial blood gas analysis 4.2.3. Alveolar Macrophages and Nitrite Release from Cultured Alveolar Macrophages 4.2.4. Cytokine concentrations in BALF 4.2.5. Cytokine concentrations in Plasma 4.3. Conclusions 5. Summary
 Zusammenfassung References Acknowledgement Lebenslauf Eherenwörtlich Erklärung
16 16 17 21 22 26 30 30 30 31 32 32 33 33 38 39 44 45
47 51 64 65 67
ABBREVIATIONS  ARDS Acute respiratory distress syndrome ALI Acute lung injury AM Alveolar macrophage BAL Bronchoalveolar lavage BALF Bronchoalveolar lavage fluid BE Base excess in plasma ELISA Enzyme-linked immunosorbent assay FiO2 of inspired oxygen Fraction hi-aft group The group of inhalation of 5.0µg IL-10 after LPS injection hi-bef group The group of inhalation of 5.0µg IL-10 before LPS injection HCO3- Plasma bicarbonate concentration HR Heart rate IQR Interquartile range IFN- Interferon-gamma IL-1ß Interleukin-1 beta IL-10 Interleukin-10 IL-1ra IL-1-receptor antagonist IL-6 Interleukin-6 IL-8 Interleukin-8 LPS Lipopolysaccharide I:E Ratio of inspiration time to expiration time iNOS Inducible nitric oxide synthase kg Kilogram lo-aft group The group of inhalation of 0.5µg IL-10 after LPS injection
lo-bef group The group of inhalation of 0.5µg IL-10 before LPS injection MAP Mean arterial blood pressure MMAD Mass median aerodynamic diameter Mea Measurement-time point during the experimental protocol mEq Milliequivalent mEq/l Milliequivalent per litre mRNA Messenger-RNA NK Natural killer cell PaCO2 carbon dioxide tension Arterial PaO2 oxygen tension Arterial PBS Phosphate buffered saline PEEP Positive end expiratory pressure pH The logarithm of the reciprocal of hydrogen-ion concentration in gram atoms per litre Pmax Peak airway pressure rhIL-10 Recombinant human IL-10 Semi-IQR Semi interquartile range TNF- Tumour necrosis factor-alpha vs. Versus  
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