The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis.
BACKGROUND
The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed serving as a connector between the nervous and immune system. This connection is called the "cholinergic inflammatory pathway." Through stimulation of the acetylcholine receptors located upon the macrophages, the "unspecific" immune system can be directly influenced.


METHODS
The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model.


RESULTS
After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals (34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis.


CONCLUSIONS
The vagal nerve is therefore an important modulator of the immune system.
Kessler
Wolfram
W
Department of Surgery, Abteilung für Allgemeine Chirurgie, Visceral-Thorax- und Gefässchirurgie, Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität, Friedrich-Loeffler-Strasse 23b, 17475, Greifswald, Germany. wkessler@uni-greifswald.de
Traeger
Tobias
T
Westerholt
Alexandra
A
Neher
Friederike
F
Mikulcak
Marlene
M
Müller
Antje
A
Maier
Stefan
S
Heidecke
Claus-Dieter
CD
D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology; D003108:Colonic Diseases / Q000276:immunology / Q000401:mortality; D004195:Disease Models, Animal; D005260:Female; D007107:Immune System / Q000294:innervation*; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007416:Intestinal Perforation / Q000276:immunology / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000276:immunology* / Q000401:mortality; D018805:Sepsis / Q000382:microbiology / Q000503:physiopathology*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014628:Vagotomy / Q000401:mortality; D014630:Vagus Nerve / Q000276:immunology*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10