Association of tumor necrosis factor, interleukin-6 and cyclooxygenase pathway with lipopolysaccharide-induced...

Many factors and mechanisms have been proposed as causes for intussusception (IN); however, the etiology remains unclear. Inflammatory mediators such as tumor necrosis factor (TNF) and interleukin-6 (IL-6), which are elevated during infectious diseases, can significantly affect gastrointestinal motility. Motility changes caused by these agents might contribute to the development of IN. The aim of this experimental study was to determine the preventive effects of indomethacin on lipopolysaccharide (LPS)-induced IN in mice and to investigate the role of TNF and IL-6 on intussusception.

Seventy-eight mice were divided into five groups. In the Control group (n=6), no procedure was done. In the Sham group (n=6), 1 ml saline, in the Indomethacin group (n=6), 10 mg/kg of indomethacin, in the LPS group (n=30), 12 mg/kg of LPS was administered intraperitoneally (IP). In the Treatment group (n=30), 10 mg/kg of indomethacin was administered IP following 12 mg/kg of LPS. All animals were laparotomized 6 hours following IP injections. The existence of IN was noted and blood specimens were obtained. TNFalpha and IL-6 plasma level measurements were performed by standard ELISA for mice. The results were compared using the Mann-Whitney U test and one-way ANOVA test. A value of p<0.05 was considered significant.

Five mice (1 in the control, 2 in the LPS, 2 in the Treatment group) were excluded from the study. IN was observed in 6 (20%) mice in the LPS group, whereas it was not found in any mice in the Treatment group. Mean TNFalpha and IL-6 levels were statistically higher in the LPS group (394.72+/-403.79; 195.18+/-218.37 pg/ml, respectively) compared to all other groups, including the Treatment group (p<0.05 for each comparison). Within the LPS group of mice, the levels were higher in animals with IN compared to the mice without IN.

Increased TNFalpha and IL-6 levels induced by LPS correlated well with the occurrence of IN, and a decrease in these levels via cyclooxygenase (COX) inhibition by indomethacin prevented IN from forming in this experimental model.