Introduction

Increased levels of pro- and anti-inflammatory cytokines were observed in various segments of histologically-intact small intestine in animal models of acute and chronic colitis. Whether these cytokines are produced locally or spread from the inflamed colon is not known. In addition, the role of gut innervation in this upregulation is not fully understood.

Aims

To examine whether cytokines are produced de novo in the small intestine in two rat models of colitis; and to investigate the role of capsaicin-sensitive primary afferents in the synthesis of these inflammatory cytokines.

Methods

Colitis was induced by rectal instillation of iodoacetamide (IA) or trinitrobenzene sulphonic acid (TNBS) in adult Sprague-Dawley rats. Using reverse transcriptase (RT) and real-time PCR, TNF-α, and IL-10 mRNA expression was measured in mucosal scrapings of the duodenum, jejunum, ileum and colon at different time intervals after induction of colitis. Capsaicin-sensitive primary afferents (CSPA) were ablated using subcutaneous injections of capsaicin at time 0, 8 and 32 h, and the experiment was repeated at specific time intervals to detect any effect on cytokines expression.

Results

TNF-α mRNA expression increased by 3-40 times in the different intestinal segments (p<0.05 to p<0.001), 48h after IA-induced colitis. CSPA ablation completely inhibited this upregulation in the small intestine, but not in the colon. Similar results were obtained in TNBS-induced colitis at 24 h. Intestinal IL-10 mRNA expression significantly decreased at 12 h and then increased by 6-43 times (p<0.05 to p<0.001) 48h after IA administration. This increase was abolished in rats subjected to CSPA ablation except in the colon, where IL-10 further increased by twice (p<0.05). In the TNBS group, there was 4-12- and 4-7-fold increases in small intestinal IL-10 mRNA expression at 1 and 21 days after colitis induction, respectively (both p<0.01). This increase was not observed in rats pretreated with capsaicin. Capsaicin-treated and untreated rats had comparable visual ulcer scores after colitis induction.

Conclusion

Inflammatory cytokines are produced de novo in distant intestinal segments in colitis. CSPA fibers play a key role in the upregulation of this synthesis.

中文翻译：

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大鼠实验性结肠炎在远离肠道的位置诱导从头合成细胞因子：对辣椒素敏感的初级传入纤维的作用。

介绍

在急性和慢性结肠炎的动物模型中，在组织学完整的小肠的各个部分中观察到促炎和抗炎细胞因子水平的升高。这些细胞因子是局部产生还是从发炎的结肠扩散尚不清楚。此外，肠神经支配在这种上调中的作用还没有被完全理解。

目的

在两种大鼠结肠炎模型中检查小肠是否从头产生细胞因子；并研究对辣椒素敏感的初级传入途径在这些炎性细胞因子合成中的作用。

方法

在成年Sprague-Dawley大鼠中，通过直肠滴入碘乙酰胺（IA）或三硝基苯磺酸（TNBS）诱发结肠炎。使用逆转录酶（RT）和实时PCR，在结肠炎诱发后的不同时间间隔，测量十二指肠，空肠，回肠和结肠的粘膜刮取物中的TNF- α和IL-10 mRNA表达。在皮下注射辣椒素在0、8和32小时消融对辣椒素敏感的初级传入（CSPA），并在特定的时间间隔重复该实验以检测对细胞因子表达的任何影响。

结果

IA引起的结肠炎后48h，不同肠段中TNF - αmRNA表达增加3-40倍（p <0.05至p <0.001）。CSPA消融完全抑制了小肠中的这种上调，但不抑制结肠中的上调。在TNBS诱导的结肠炎中，在24小时时获得了类似的结果。IA给药后48小时，肠道IL-10 mRNA表达显着下降，然后上升6-43倍（p <0.05至p <0.001）。在接受CSPA消融的大鼠中，除了结肠中IL-10进一步增加了两倍（p<0.05）。在TNBS组中，结肠炎诱导后1天和21天，小肠IL-10 mRNA表达分别增加了4-12倍和4-7倍（均p <0.01）。在用辣椒素预处理的大鼠中未观察到这种增加。诱导结肠炎后，用辣椒素治疗和未治疗的大鼠的视觉溃疡评分相当。

结论

炎性细胞因子在结肠炎的远处肠段重新产生。CSPA纤维在该合成的上调中起关键作用。