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Infiammazione Nutrizione

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Infiammazione Nutrizione

  1. 1. Cori cycle with sources of gluconeogenic substrates. Tumours produce factors such as lipid-mobilizing factor (LMF), which induces breakdown of adipose tissue into fatty acids, and proteolysis-inducing factor (PIF), which induces protein degradation (amino acids) in skeletal muscle. Tumour necrosis factor (TNF)-  also contributes to these processes. These are important gluconeogenic substrates that can be used in acute-phase protein (APP) synthesis by the liver. Tumours convert glucose to lactate, which is transferred to the liver, where it is converted back into glucose. This cycle uses a large amount of energy, and might contribute to cachexia.
  2. 2. Interactions between pro-inflammatory cytokines and PIF
  3. 3. MUSCLE WASTE AND ACUTE-PHASE RESPONSE IL-6, TNF, IL- 1 , IFN-  PROTEINS  AA ACUTE PHASE PROTEINS AA  PROTEIN DEGRADATION THE MOST PARADIGMATIC METABOLIC DERANGEMENTS INDUCED BY THE TUMOR ARE THE ACTIVATION OF PROTEOLYSIS IN SKELETAL MUSCLE AND THE REDISTRIBUTION OF PROTEIN SYNTHESIS IN THE LIVER (  SYNTHESIS OF ALBUMIN, ETC AND  CRP, ETC). THESE ALTERATIONS CAN BE INDUCED BY DIFFERENT CYTOKINES From Tisdale “Cachexia in Medicine” 2004
  4. 7. Ruolo degli EPA <ul><li> Risposta infiammatoria </li></ul><ul><li> Produzione di citochine pro-infiammatorie </li></ul><ul><li>APPR attenuata </li></ul><ul><li> Livelli / attività dei fattori che inducono proteolisi (PIF) </li></ul><ul><li>Diminuzione della perdita di peso correlata al tumore </li></ul><ul><li>Aumento della sopravvivenza </li></ul>
  5. 8. Evidenze cliniche
  6. 9. EPA per os nel pz. oncologico <ul><li>Prolungata sopravvivenza </li></ul><ul><li>Significativo miglioramento nel Karnofsky performance status </li></ul><ul><li>Diminuzione della produzione di TNF dopo assunzione di olio di pesce </li></ul>Adapted from Gogos, 1998 Cancer 82:395 Placebo Max epa p<0.025 n=60 800 600 400 200 0 100 80 60 40 20 0.0 Survival (days) Cumulative Survival (%)
  7. 10. Modificazioni di peso e LBM dopo 8 settimane nel gruppo con omega 3 vs gruppo di controllo 0.09 1.21 0.46 1.46 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 weight LBM kg p = NS Fearon et al 2003 n = 30 n = 26 n = 28 n = 22 EXP Controls
  8. 11. Variazioni della LBM conseguenti ad EPA nel tumore pancreatico. cans LBm (kg) EXP: p = 0,036 r = 0,332 Controlli = NS Fearon et al 2003

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