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IL-6, TNF-α, and iNOS is associated with decreased colonic contraction in rats with multiple organ dysfunction
Ang Li1, Junjie Xiong, Zheyu Chen
1Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Background:
Gastrointestinal stasis is frequently accompanied by multiple organ dysfunction syndrome (MODS), which may lead to gastrointestinal smooth muscle dysfunction. The aim of this study is to investigate whether MODS initiates an inflammatory response and produces IL-6, TNF-α, and iNOS cytokines, as well as to determine whether these cytokines give rise to gastrointestinal smooth muscle dysfunction.
Materials And Methods:
Sixty Wistar rats were divided equally into a negative control group, a positive control group, and a MODS group. The number of stool spots, the contractility of muscle strips in the colon, and morphologic changes to the colon smooth muscle were recorded. The mRNA and protein expressions of IL-6, TNF-α, and iNOS in the colon were detected by semiquantitative reverse transcription polymerase chain reaction and immunohistochemistry respectively. In addition, the NO level was observed.
Results:
For the MODS group, the colon stool numbers, maximal contractive stress, and spontaneous frequency of muscle strips were, respectively, 0.77 ± 0.52 pill/h, 301g/cm(3), and 11.52 ± 0.38 contractions/min (P < 0.05); for the negative control group, 1.54 ± 0.64 pills/h, 645 g/cm(3), and 19.2 ± 0.71 contractions/min, respectively (P < 0.05); and for the positive control group, 0.94 ± 0.21 pills/h, 415 g/cm(3), and 14.1 ± 0.52 contractions/min, respectively (P < 0.05). In the MODS group, there was a marked up-regulation of expression of IL-6, TNF-α, and iNOS and the contractility of the smooth muscle strips had a negative correlation with the expression of IL-6, TNF-α, and iNOS.
Conclusion:
We speculate that reduced colon motility in the MODS rats may be related to the increase in iNOS, IL-6, and TNF-α in the colon muscularis.
Insights
Multiple organ dysfunction syndrome (MODS) in rats leads to gastrointestinal stasis by increasing inflammatory cytokines, specifically interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS), impairing colon motility.
Area of Science:
- Gastroenterology
- Immunology
- Physiology
Background:
- Gastrointestinal stasis often accompanies multiple organ dysfunction syndrome (MODS), potentially causing gastrointestinal smooth muscle dysfunction.
- This study investigates the inflammatory mechanisms linking MODS to gastrointestinal dysfunction.
Purpose of the Study:
- To determine if MODS triggers an inflammatory response producing IL-6, TNF-α, and iNOS.
- To ascertain if these cytokines contribute to gastrointestinal smooth muscle dysfunction.
Main Methods:
- Wistar rats were divided into control and MODS groups.
- Colon motility, smooth muscle contractility, and morphology were assessed.
- Expressions of IL-6, TNF-α, and iNOS mRNA and protein, along with NO levels, were quantified.
Main Results:
- MODS rats exhibited significantly reduced stool output and colon smooth muscle contractility compared to controls.
- A marked upregulation of IL-6, TNF-α, and iNOS was observed in the MODS group.
- Smooth muscle contractility negatively correlated with the expression levels of these inflammatory cytokines.
Conclusions:
- Increased iNOS, IL-6, and TNF-α in the colon muscularis are implicated in reduced colon motility observed in MODS rats.
- These findings suggest a cytokine-mediated mechanism for gastrointestinal dysfunction in MODS.
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