Stimulation of acetylcholine receptors impairs host defence during pneumococcal pneumonia.
The cholinergic nervous system can inhibit the systemic inflammation accompanying sepsis by virtue of a specific action of acetylcholine on alpha7 cholinergic receptors. The current authors sought to determine the effect of nicotine, an alpha7 cholinergic receptor agonist, on the host response to pneumonia caused by Streptococcus pneumoniae. Mice were intranasally infected with S. pneumoniae and treated with nicotine or saline intraperitoneally using a treatment schedule shown to improve host defence 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 h after infection. At 48 h after infection, bacterial burdens had increased in both treatment groups and differences were no longer present. Remarkably, mice treated with nicotine showed enhanced lung inflammation at 24 h after infection. Moreover, both lung and plasma concentrations of the pro-inflammatory cytokines tumour necrosis factor-alpha and interferon-gamma were higher in nicotine-treated animals at this time-point. Additional studies examining the effect of nicotine on the immediate (4-h) inflammatory response to S. pneumoniae did not reveal an anti-inflammatory effect of nicotine either. The present data suggest that nicotine transiently impairs host defence in pneumococcal pneumonia.
Giebelen
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Academic Medical Center, Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl
Leendertse
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Florquin
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van der Poll
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D000818:Animals; D018925:Chemokines / Q000378:metabolism; D005260:Female; D007107:Immune System; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000378:metabolism* / Q000382:microbiology; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018925:Chemokines; C579166:Chrna7 protein, mouse; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine