Darm als Immunorgan - AKE
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Der Darm als immunologisches Organ Herbert Lochs Innsbruck [email protected] Oberfläche 300m² Nervenzellen 108 Bakterien 1014 Immunzellen 50% Blutfluss 25 - 40% Energieumsatz 40% Proteinsynthese 50% [email protected] Funktionen des Darmes • Resorption – 10-12 l Wasser, Elektrolyte, 2- 3000 kcal, 50 – 100 g Protein • Sekretion – 7- 8 l Wasser, Elektrolyte, 1 Liter 1N HCl, Bicarbonat Enzyme, IgA, Mucine, Hormone • Motilität, Sensorik, Vasomotorik • Barriere, • Immunfunktion [email protected] Darm als Immunorgan • Barriere – Struktur, Funktion, Regelung • Immunreaktion – Homöostase, Infektion, Allergie • Veränderungen bei Krankheit • Therapeutische Möglichkeiten [email protected] Intestinale Barriere - Struktur Santvoort et al., Surgery 2008 • Luminal Flora • Mucus – Mucines, IgA, – Defensines • Epithelium – Cells, – Tight Junctions • GI Immune System – Tolerance/Allergy – Innflammation – Immuno deficiency [email protected] Intestinale Immunabwehr Abreu Nat. Rev. Immun. 2010 [email protected] Antigen Aufnahme im Darm A. Mowat Nat. Rev. 2003 [email protected] Dendritic Cells on the tip of Villi Chieppa et al. J. Exp. Med. 2006 [email protected] GI Immunreaktion A. Mowat, Nat. rev. 2003 Immuntoleranz: TReg, IL10, IFNγ, TGFβ Immunabwehr: TLR, IL12, TH1,IFNγ, [email protected] Intestinale Barriere - Störungen Santvoort et al., Surgery 2008 • Flora • Dysbiose, • Pathogene Keime • Mucus – Mucine, IgA, – Defensine • Epithel – Atrophie – TJ leck – Invasion von Immunzellen • GI Immunsystem – Entzündung – Anergie [email protected] Intestinale Barriere Sansonetti, Nat. Immun. 2004 [email protected] Sartor, Gastro 2008 Immunreaktion Darm Sartor Gastro 2008 [email protected] Mucosal biofilm in CHF Sandek et al., J. Am. Coll. Card. 2007 Highly colonised large intestinal mucosa Low colonised large intestinal mucosa Controls Chronic heart failure [email protected] Intestinale Barriere Darm – Mesenteriale Lymphknoten – Leber - Milz [email protected] Gut in SIRS – Sepsis Reduced Mucosal Oxygen Saturation Inflammation Cytotoxicity Mucosal Ischemia Disturbed Barrier Translocation of Bacteria, Toxins [email protected] Darm als Immunorgan • Barriere – Struktur, Funktion, Regelung • Immunreaktion – Homöostase, Infektion, Allergie • Veränderungen bei Krankheit • Therapeutische Möglichkeiten [email protected] Stress and bacterial Adherence Söderholm et. al. Gastro 2002 [email protected] Citrobacter- Changes in Mucosal Structure Wu et al., AJP 2008 Control Citrobacter S. Boulardii Citrobacter + S. Boulardii [email protected] Secretory IgA - Effect of Starvation and Steroid Stress Spitz et. al., Crit. Care Med 1996 [email protected] Endotoxemia in chronic heart disease Sharma R et al, Am J Cardiol 2003; 92: 188-193 [email protected] Mucosal blood Flow in Sepsis Care Med. 2008 [email protected] Dubin et al. Crit. Fecal Flora in SIRS Shimizu et al. J. Trauma 2006 [email protected] Intestinal Flora in Critical Illness Clark et al. Shock 2007 [email protected] Effect of Antibiotics on mucosal Flora Swidsinski et al., Arch. Med. Res 2008 20 days after antibiotics UC Patient during therapy with metronidazol and ciprofloxacin No antibiotics [email protected] Enteral Nutrition – IgA Ohta et. al. A.J.Surg 2003 parenteral enteral [email protected] Enteral Nutrition intestinal Barrier in hemorrhagic Shock Luyer et. al. Shock 2004 Starved 16,7% Fat 52,2% Fat [email protected] Effect of Nutrition on Fecal Flora Schneider et al., Eur. J. Nutr. 2000 [email protected] Effect of Bacteria on tight junctions Otte et. al. AJP 2004 Control S. Dublin [email protected] Pretreatment E. Coli Nissle Inflammation - Bact. Fragilis Round et al. Nat. Rev. Immun. 2009 [email protected] Synbiotika – Infektionsprophylaxe perioperativ Probiotika % Infektionen 100 Kontrolle n= 77 103 90 80 60 n= 90 105 66 129 137 50 54 101 40 20 0 a s a n X X ra ry ht w m iti o a T T TS e t I g a u s L L w a g z r t u a r e a re tr ga es es na d gh N y k Su u y y l a n u c n a a S a K A P M R R Po es N i y h c a la M ss R O a p m za t o K [email protected] in a J S IT Synbiotics in Trauma Patients Kotzampassi et al., WJS 2006 65 Patients with severe Trauma, 15 days , Synbiotic vs. Placebo [email protected] Vagal Stimulation maintains Barrier in Burns Costantini et al., J. Trauma 2010 Control Burn + Vagal Stimulation [email protected] Burn Burn + Vagal Stimulation, Vagotomy Darm Immunorgan SIRS und Sepsis • Dysbiose • Schleimhautatrophie • Immunabwehr??? • Circulus vitiosus • Enterale Ernährung • Stresstherapie • Probiotika [email protected] Darm als Immunorgan • Extrem wichtig, extrem empfindlich • Ursachen für Störung – Stress, Schock, Katecholamine, Antibiotika – Infektionen, Fasten, Alter • Diagnostik – Entzündungsparameter, LPS • Therapie – Ernährung, Probiotika, Stressreduktion [email protected]