The effect of the cholinergic anti-inflammatory pathway on experimental colitis

Abstract

Recent studies have reported that neuroimmune interaction can affect the process of intestinal inflammation. The cholinergic anti-inflammatory pathway is a neural mechanism that is controlled by the vagus nerve, and inhibits proinflammatory cytokine overproduction in inflammatory response. Inflammatory bowel diseases (IBD) are characterized by proinflammatory cytokines, tissue damage, and loss of neuron in inflamed mucosa, which implies the cholinergic anti-inflammatory pathway is destroyed during the process of inflammatory response. In the study, we studied the effect of cholinergic agonist as anabaseine and nicotinic receptor antagonist as chlorisondamine diiodide on TNBS-induced colitis, to investigate the potential therapeutic effect of the cholinergic anti-inflammatory pathway on IBD. Trinitrobenzene sulfonic acid (TNBS)-induced colitis was produced, 10μg anabaseine or 1.5μg chlorisondamine diiodide was administrated i.p to each mouse half an hour before the induction of colitis, and repeated on interval day till the mice were sacrificed. Inflammation was examined by histological analysis, myeloperoxidase (MPO) activity, and the production of proinflammatory cytokines as TNF-α, IL-1β in colonic tissue. The expression of neuronal marker as S100 protein and neurofilament protein was determined by immunohistochemistry. The mice with colitis treated by anabaseine showed less tissue damage, less MPO activity, and less proinflammatory cytokine level, compared with those mice with colitis untreated, whereas the mice with colitis treated by chlorisondamine diiodide showed worst tissue damage, highest MPO activity, and highest proinflammatory cytokine level. The expression of S100 protein and neurofilament protein was absent in inflammatory mucosa of mice with TNBS-induced colitis or those treated by chlorisondamine diiodide. However, administration with anabaseine restored the expression of those neuronal markers in inflammatory mucosa of mice with TNBS-induced colitis, and protected the mucosal neuron file from loss. Our data shows the agonist of the cholinergic anti-inflammatory pathway inhibits colonic inflammatory response by down-regulating the production of proinflammatory cytokines, and inhibiting loss of mucosal neuron, which suggests that modulating the cholinergic anti-inflammatory pathway may be a new potential management for inflammatory bowel diseases.