title: Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?
abstract: BACKGROUND
  The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the α-7-nicotinic acetylcholine receptor (α7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and chronic inflammation are both linked to poor outcome in dialysis patients. The aim of this study was to investigate CAP activity in these patients.
  
  
  METHODS
  Twenty dialysis patients, 12 hemodialysis (HD) and 8 peritoneal dialysis (PD) patients (12 male, 8 female; age range 47-83 years) and 8 controls (5 male, 3 female; age range 31-52 years) were analyzed for C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1b (IL-1b), IL-6 and IL-10 at baseline. The cytokines were then assessed after whole blood stimulation ex vivo with lipopolysaccharide (LPS) (10 and 100 ng/mL) and again in the presence of 45 and 90 μmol/L GTS-21, a cholinergic α7nAChR agonist.
  
  
  RESULTS
  CRP, TNF, IL-1 and IL-6 were significantly higher, whereas IL-10 was significantly lower at baseline in patients compared with controls. After LPS stimulation, TNF increased significantly more in patients than in controls but decreased to similar levels in both groups after addition of GTS-21. IL-6 attenuation was comparable with TNF and the IL-1b pattern was similar but remained significantly higher in patients. Interestingly, IL-10 increased after GTS-21 in a dose-dependent manner, but only in patients. Results in HD and PD patients did not differ.
  
  
  CONCLUSIONS
  The response of immune cells after LPS exposure and cholinergic stimulation suggests a functional CAP in dialysis patients. It may thus be possible to target the α7nAChR control of cytokine release as an anti-inflammatory strategy and thereby improve outcome in these patients.
authors.affiliation: Renal Medicine and Baxter Novum , CLINTEC, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Hilderman
authors.affiliation: Renal Medicine and Baxter Novum , CLINTEC, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Qureshi
authors.affiliation: Center for Biomedical Science , Feinstein Institute for Medical Research , Manhasset, NY , USA.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Al-Abed
authors.affiliation: Royal Institute of Technology , School of Technology and Health , Stockholm , Sweden.
authors.forename: Farhad
authors.initials: F
authors.lastname: Abtahi
authors.affiliation: Royal Institute of Technology , School of Technology and Health , Stockholm , Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Lindecrantz
authors.affiliation: Renal Medicine and Baxter Novum , CLINTEC, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Anderstam
authors.affiliation: Renal Medicine and Baxter Novum , CLINTEC, Karolinska Institutet , Stockholm , Sweden.
authors.forename: Annette
authors.initials: A
authors.lastname: Bruchfeld
keywords: autonomic dysfunction; cholinergic agonist; cytokine attenuation; dialysis; inflammation