he Vagus Nerve: A Tonic Inhibitory Influence Associated With Inflammatory Bowel isease in a Murine Model

D d M S v ackground & Aims: The recently proposed Inflammatory eflex describes an interaction between the vagus nerve and eripheral macrophages, resulting in attenuation of proinflamatory cytokine release in response to systemic exposure to acterial endotoxin. The purpose of this study was to determine hether a similar vagus/macrophage axis modulates the inammatory responses in the colon in mice. Methods: We ssessed the Disease Activity Index (DAI), macroscopic and istologic damage, serum amyloid-P level, and myeloperoxidase ctivity in colitis induced by administration of dextran sodium ulfate (DSS) in healthy and vagotomized C57BL/6 and in mice eficient in macrophage-colony stimulating factor (M-CSF)– nduced and in hapten-induced colitis. A pyloroplasty was perormed in vagotomized mice. Results: DAI, macroscopic and istologic scores, myeloperoxidase activity, levels of serum amyoid-P, and colonic tissue levels of interleukin (IL)-1 , IL-6, and umor necrosis factorwere increased significantly in vagotoized mice 5 days post-DSS and 3 days after hapten-induced olitis compared with sham-operated mice that received DSS or he hapten. Pretreatment with nicotine significantly decreased ach of these markers in vagotomized mice with DSS colitis, and ll markers except DAI and IL-6 in sham-operated DSS-treated ice. Conversely, hexamethonium treatment significantly inreased each of these markers in the sham-operated DSS-treated ice. Vagotomy had no effect on the colitis in M-CSF–deficient ice. Conclusions: The vagus nerve plays a counterinflammaory role in acute colitis via a macrophage-dependent mechanism, nvolving hexamethonium-sensitive nicotinic receptors. The idenification of a counterinflammatory neural pathway would open ew therapeutic avenues for treating acute exacerbations of inammatory bowel disease.