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|
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result sql = Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice.
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result sql = Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short- and long-term leptin replacement therapy. Short-term leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.
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result sql = Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice.
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char = r;code = 114
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char = e;code = 101
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char = e;code = 101
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char = i;code = 105
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char = e;code = 101
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char = r;code = 114
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char = p;code = 112
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char = t;code = 116
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char = t;code = 116
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char = ;code = 32
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char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
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char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = s;code = 115
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char = d;code = 100
char = ;code = 32
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char = o;code = 111
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char = p;code = 112
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char = i;code = 105
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char = a;code = 97
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = p;code = 112
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = b;code = 98
char = s;code = 115
char = e;code = 101
char = n;code = 110
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char = ;code = 32
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char = n;code = 110
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char = u;code = 117
char = c;code = 99
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char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
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char = e;code = 101
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char = t;code = 116
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char = t;code = 116
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char = e;code = 101
char = d;code = 100
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char = ;code = 32
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char = e;code = 101
char = l;code = 108
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char = ;code = 32
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char = P;code = 80
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = b;code = 98
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = y;code = 121
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result sql = Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short- and long-term leptin replacement therapy. Short-term leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.
Publication: Proc. Natl. Acad. Sci. U.S.A. 2008 Jun 10 ;105(23)::8085-90. :doi: 10.1073/pnas.0804091105.
Publication Date: 2008 Jun 10
Study Author(s): Sennello, Joseph A;Fayad, Raja;Pini, Maria;Gove, Melissa E;Ponemone, Venkatesh;Cabay, Robert J;Siegmund, Britta;Dinarello, Charles A;Fantuzzi, Giamila;
Institution: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
Shortcut link to this study:
Publication Date: 2008 Jun 10
Study Author(s): Sennello, Joseph A;Fayad, Raja;Pini, Maria;Gove, Melissa E;Ponemone, Venkatesh;Cabay, Robert J;Siegmund, Britta;Dinarello, Charles A;Fantuzzi, Giamila;
Institution: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
Shortcut link to this study:
Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short- and long-term leptin replacement therapy. Short-term leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.
PMID: 18515422
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