The cholinergic anti-inflammatory system limits T cell infiltration into the neurodegenerative CNS, but cannot counteract complex CNS inflammation.

Stimulation of the nicotinic alpha7 acetylcholine receptor (nAChRalpha7) by nicotine or acetylcholine initiates the cholinergic anti-inflammatory pathway, a mechanism for neural inhibition of inflammation. The action of this pathway was initially discovered in animal models of endotoxemia and septic shock, and later described in a number of other diseases. Moreover, the action of this pathway is also implied in human degenerative diseases of the central nervous system (CNS) like amyotrophic lateral sclerosis or Alzheimer's disease. In spite of this general interest, little is known about its involvement in regulating T cell entry into, or inflammatory reactions within the CNS. We tested the action of the cholinergic anti-inflammatory pathway in nAChRalpha7-deficient mice and their wildtype counterparts in two different experimental settings: In the facial nerve axotomy model characterized by neurodegeneration and T cell infiltration, and in the experimental autoimmune encephalomyelitis (EAE) model providing a very complex scenario of CNS inflammation and demyelination. We found that the cholinergic anti-inflammatory pathway limits the site-directed influx of activated T cells into the lesioned facial motor nucleus, but cannot counteract CNS inflammation in EAE.