Spleen vagal denervation inhibits the production of antibodies to circulating antigens

PLoS One. 2008 Sep 5;3(9):e3152. doi: 10.1371/journal.pone.0003152.


Background: Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output.

Methodology/principal findings: This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA) does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS), activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA.

Conclusions/significance: These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism*
  • Brain / metabolism
  • Corticosterone / metabolism
  • Denervation
  • Herpesvirus 1, Suid / metabolism
  • Immune System
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / pharmacology
  • Models, Anatomic
  • Neurosurgical Procedures
  • Ovalbumin / chemistry
  • Parasympathetic Nervous System / metabolism
  • Rats
  • Spleen / immunology*
  • Spleen / innervation*
  • Spleen / physiology
  • Vagus Nerve / pathology*


  • Antigens
  • Lipopolysaccharides
  • Ovalbumin
  • Corticosterone