ABSTRACT
PURPOSE: Major surgery can modulate the immune system and by this the clinical course of following complications. Effects of minor surgical treatments on the immune system and septic complications are poorly understood. MATERIALS AND METHODS: We investigated the effect of a minor surgical procedure--the implantation of an osmotic pump--on the outcome of experimental polymicrobial sepsis (colon ascendens stent-induced peritonitis, CASP) in mice. RESULTS: Animals with pumps implanted 3 days prior to CASP showed an attenuated clinical course of sepsis and increased survival. While measured serum cytokine levels were not affected by the minor surgical stress of pump implantation, splenocyte secretion of IFN-gamma in response to lipopolysaccharide was increased. CONCLUSION: The early implantation of alloplastic material modulates the immune system and leads to an increased survival of a polymicrobial sepsis. Identifying the molecular nature of this effect might point the way to a new therapeutic approach to reduce sepsis mortality.
Subject(s)
Disease Models, Animal , Immunocompetence/immunology , Prosthesis Implantation , Sepsis/immunology , Sepsis/prevention & control , Animals , Chemokines/blood , Chemokines/immunology , Colon, Ascending , Cytokines/blood , Cytokines/immunology , Down-Regulation/immunology , Female , Inflammation/immunology , Lipopolysaccharides/adverse effects , Lipopolysaccharides/immunology , Mice , Mice, Inbred C57BL , Peritonitis/prevention & control , Sepsis/mortality , Severity of Illness Index , Single-Blind Method , Spleen/cytology , Statistics, Nonparametric , Stents , Survival Rate , Time Factors , VagotomyABSTRACT
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. CONCLUSION: The vagal nerve is therefore an important modulator of the immune system.
