The Impact Of Laparoscopy And Laparotomy Surgery On TLR4Signal Pathway In Children With Appendicitis

Objective: Surgery is a special form of trauma that may affect patients’ postoperativerecovery, by causing local tissue damage as well as systemic stress response. Althoughprevious studies have shown that the function of the immune system is closely related tothe degree of stress response, further research is required for the exact mechanism. Thisstudy aims to discuss the effects of stress response caused by different kinds of surgery onTLR-mediated innate immune response by comparing the changes in TLR signals inchildren with appendicitis preoperatively and postoperatively.Methods:39children with acute appendicitis were selected,17of whom hadlaparoscopic appendectomy (group LA) and22had open appendectomy (group OA).Peripheral blood samples of3ml each were collected respectively before, after and one dayafter appendectomy to measure C-reactive protein (CRP), tumor necrosis factor-ɑ (TNF-ɑ)and interleukin-6(IL-6) in plasma, the levels of CD14, MD-2and TLR4on monocytes ateach time point by flow cytometry, as well as the intracellular activity of p38, ERK1/2andStat3after LPS stimulation. Meanwhile, the production of TNF-a and IL-6in thesupernatant after stimulation was measured.Results:1.In group LA, the levels of CRP, TNF-ɑ, and IL-6in postoperative plasmasamples were significantly higher than those in the preoperative samples. They were alsohigher, though down-regulated, than those in the samples taken one day postoperatively. Ingroup OA, the levels of CRP, TNF-ɑ, and IL-6in plasm had the same changes as in groupLA, but they were still higher than those in group LA, when the samples were collectedpreoperatively and one day postoperatively.2. In group LA, MD-2and TLR4were significantly decreased postoperatively, andrecovered one day postoperatively. In group OA, these receptors had the same changes as in group LA, but were significantly lower than those in group LA(P<0.05）postoperatively.In addition, CD14levels did not change much in group LA, while they significantlydecreased in group OA and recovered one day postoperatively.3. In group LA, no differences were found in the activities of p38, ERK1/2, Stat3inmonocytes preoperatively and postoperatively. But in group OA, these intracellular signalswere significantly suppressed postoperatively and recovered one day postoperatively. Thelevels of p38, ERK1/2, Stat3in group OA were significantly lower than those in group LApostoperatively.4. In group LA, TNF-ɑ and IL-6were abundantly expressed in blood samples afterLPS stimulation, and there were no differences at different time points postoperatively.However, those factors in group OA were significantly decreased at postoperative point(p<0.05), and were recovered one day postoperatively. The cytokines induced by LPS ingroup OA were significantly lower than those in group LA postoperatively.Conclusion:1. Transient systemic inflammation can be caused by appendectomy, butit was less sever by laparoscopy than by laparotomy.2. Laparotomy may cause the decreased expression levels of CD14, MD-2and TLR4on monocytes, but the stress response was relieved to a certain extent in LA group.3. Open appendectomy can inhibit the activation of TLR4signaling pathway inmonocytes upon LPS stimulation, which may result in the insufficient amount of TNF-ɑand IL-6during postoperative infection, while laparoscopy surgery can reduce the sideeffect to some extent.