Stimulation of acetylcholine receptors impairs host defense during pneumococcal pneumonia

¹ Center for Infection and Immunity Amsterdam (CINIMA); and Center for Experimental and Molecular Medicine
² Dept of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

^* To whom correspondence should be addressed. E-mail: t.vanderpoll{at}amc.uva.nl.

	Abstract

The cholinergic nervous system can inhibit the systemic inflammation accompanying sepsis by virtue of a specific action of acetylcholine on 7 cholinergic receptors. We here sought to determine the effect of nicotine, a 7 cholinergic receptor agonist, on the host response to pneumonia caused by Streptoccocus pneumoniae.

Mice were intranasally infected with S. pneumoniae and treated with nicotine or saline intraperitoneally using a treatment schedule shown to improve host defense against abdominal sepsis.

Nicotine treatment was associated with a transiently enhanced growth of S. pneumoniae, as indicated by higher bacterial loads in both lungs and blood at 24 hours after infection. At 48 hours after infection, bacterial burdens had increased in both treatment groups and no differences were present anymore. Remarkably, mice treated with nicotine showed enhanced lung inflammation at 24 hours after infection. Moreover, both lung and plasma concentrations of the proinflammatory cytokines tumour necrosis factor- and interferon- were higher in nicotine treated animals at this time point. Additional studies examining the effect of nicotine on the immediate (4 hours) inflammatory response to S. pneumoniae did not reveal an anti-inflammatory effect of nicotine either.

These data suggest that nicotine transiently impairs host defense in pneumococcal pneumonia.