Mesenteric Lymph Collected during Peritonitis or Sepsis Potently Inhibits Gastric Motility in Rats
Abstracts
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Gastrointestinal motility and transit is strongly inhibited following an acute insult to the GI tract, such as surgery, peritonitis or sepsis. Recently it has been shown that pro-inflammatory cytokines released into mesenteric lymph during an acute insult to the GI tract mediate systemic responses (Deitch EA, Curr Opin Crit Care 2001). Aim: To determine whether mesenteric lymph collected during an acute insult to the GI tract inhibits gastric motility. Methods: Mesenteric lymph was obtained from awake lymph fistula rats, 24 h after recovery from fistula implantation during intestinal perfusion of dextrose/electrolyte solution. Lymph was collected from 3 experimental groups: vehicle (saline, 1ml, ip, n=6), peritonitis produced by acetic acid (0.5%, 1 ml, ip, n=6), and sepsis produced by lipopolysaccharide (LPS, 5mg/kg, 1ml, ip, n= 6). Lymph was collected for 12 h following treatment. Inhibition of gastric motility was measured manometrically in urethane-anesthetized recipient rats to injection of lymph (1ml) into the jugular vein (n=10 per group). Quantitative PCR for TNFa gene expression in the jejunum was measured in vehicle-treated rats (t=0h, n=2) and in LPS-treated rats 2h, 12h, and 24h (n=3/group) after injection. Results: Mesenteric lymph flow significantly increased after acetic acid or LPS treatment (average hourly lymph flow ml; vehicle 2.45 +/- 0.04; acetic acid 2.67 +/- 0.07; LPS 3.25 +/- 0.1, p<0.01 vs vehicle). Injection of acute insult lymph collected during peritonitis or sepsis produced a significant and prolonged inhibition of gastric motility in recipient rats: (decrease intragastric pressure cmH2O and duration of inhibition; control lymph: 0.14 +/- 0.05, 1.89 +/- 1.31 min; peritonitis lymph: 0.56 +/- 0.06, 9.9 +/- 0.9 min; sepsis lymph: 0.51 +/- 0.05, 6.9 +/- 0.6 min, p<0.001 vs control). TNFa gene expression in the jejunum increased after LPS injection over 90 fold compared to vehicle injection within the first two hours and decreased thereafter (relative TNFa mRNA transcription: control 1.0 +/-0.05; LPS 2h: 91.9 +/- 0.6, p<0.001; 12h: 24.7 +/- 16.8, NS, 24h: 7.0 +/- 0.4, NS). Conclusions: Mediators in mesenteric lymph, possibly cytokines, may be responsible for inhibition of gastric motility after an acute insult to the GI tract. Since the composition of lymph reflects the interstitial fluid, mediators released into the interstitium during gut injury may be transported via lymph to distant sites to alter GI and other visceral function. Supported by NIH DK 41004; DFG GL 311/1-1 |
