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Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?

Hilderman M, Qureshi AR, Al-Abed Y, Abtahi F, Lindecrantz K, Anderstam B, Bruchfeld A - Clin Kidney J (2015)

Bottom Line: CRP, TNF, IL-1 and IL-6 were significantly higher, whereas IL-10 was significantly lower at baseline in patients compared with controls.IL-6 attenuation was comparable with TNF and the IL-1b pattern was similar but remained significantly higher in patients.Results in HD and PD patients did not differ.

View Article: PubMed Central - PubMed

Affiliation: Renal Medicine and Baxter Novum , CLINTEC, Karolinska Institutet , Stockholm , Sweden.

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.

No MeSH data available.


Related in: MedlinePlus

IL-10 levels (A) after LPS: 0, 10 and 100 ng/mL; (B) after GTS-21: 45 μmol/L; and (C) 90 μmol/L in dialysis patients and controls. **P < 0.01. All samples except basal incubated for 4 h.
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SFV074F5: IL-10 levels (A) after LPS: 0, 10 and 100 ng/mL; (B) after GTS-21: 45 μmol/L; and (C) 90 μmol/L in dialysis patients and controls. **P < 0.01. All samples except basal incubated for 4 h.

Mentions: IL-1b was significantly increased in patients at the two LPS concentrations compared with controls. In both groups, IL-1b decreased in the presence of GTS-21, but a statistical difference remained between groups, with higher levels in patients (Figure 3A–C). The IL-6 pattern was similar to TNF at maximal stimulation with LPS, but again with comparable cytokine suppression with GTS-21 in both groups (Figure 4A–C). Finally, IL-10 representing an anti-inflammatory cytokine increased in the presence of GTS-21 in a dose-dependent manner, but only in patients (Figure 5A–C).Fig. 3.


Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?

Hilderman M, Qureshi AR, Al-Abed Y, Abtahi F, Lindecrantz K, Anderstam B, Bruchfeld A - Clin Kidney J (2015)

IL-10 levels (A) after LPS: 0, 10 and 100 ng/mL; (B) after GTS-21: 45 μmol/L; and (C) 90 μmol/L in dialysis patients and controls. **P < 0.01. All samples except basal incubated for 4 h.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581391&req=5

SFV074F5: IL-10 levels (A) after LPS: 0, 10 and 100 ng/mL; (B) after GTS-21: 45 μmol/L; and (C) 90 μmol/L in dialysis patients and controls. **P < 0.01. All samples except basal incubated for 4 h.
Mentions: IL-1b was significantly increased in patients at the two LPS concentrations compared with controls. In both groups, IL-1b decreased in the presence of GTS-21, but a statistical difference remained between groups, with higher levels in patients (Figure 3A–C). The IL-6 pattern was similar to TNF at maximal stimulation with LPS, but again with comparable cytokine suppression with GTS-21 in both groups (Figure 4A–C). Finally, IL-10 representing an anti-inflammatory cytokine increased in the presence of GTS-21 in a dose-dependent manner, but only in patients (Figure 5A–C).Fig. 3.

Bottom Line: CRP, TNF, IL-1 and IL-6 were significantly higher, whereas IL-10 was significantly lower at baseline in patients compared with controls.IL-6 attenuation was comparable with TNF and the IL-1b pattern was similar but remained significantly higher in patients.Results in HD and PD patients did not differ.

View Article: PubMed Central - PubMed

Affiliation: Renal Medicine and Baxter Novum , CLINTEC, Karolinska Institutet , Stockholm , Sweden.

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.

No MeSH data available.


Related in: MedlinePlus