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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• Gesundheit

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• Publié par: goethe_universitat_frankfurt_am_main
• Publié le: 01 janvier 2007
• Nombre de lectures: 39
• Langue: English

Extrait

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 ThThu Hin and daughter Nguyn Hà Qunh Anh

and to the memories of my father Prof. Nguyn Hu Mô and my mother Thch ThLi.

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 FiO 2  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 HCO 3-  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 PaCO 2  carbon dioxide tension Arterial PaO 2  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 P max  Peak airway pressure rhIL-10 Recombinant human IL-10 Semi-IQR Semi interquartile range TNF- Tumour necrosis factor-alpha vs. Versus