Z Gastroenterol 2005; 43 - P111
DOI: 10.1055/s-2005-919885

Altered Response of Peripheral Blood Mononuclear Cells to Substance P Stimulation in Patients with Irritable Bowel Syndrome;

T Liebregts 1, B Adam 1, M Meziroglu 1, K Saadat-Gilani 2, A Roeth 3, W Siffert 4, G Holtmann 1
  • 1Dept of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, University of Adelaide, Australien, Adelaide, Australien
  • 2Department of Gastroenterology and Hepatology, Essen
  • 3Department of Internal Medicine, Division of Hematology, University Hospital Essen, Essen
  • 4Institute of Pharmacology, University Hospital Essen, Essen

Aims: Transient infections are known to alter visceral sensory function and precipitating the onset of symptoms in patients with irritable bowel syndrome (IBS). Substance P (SP) plays a central role in the interaction of immune cells and visceral afferents mediated via G-protein coupled receptors. A G-protein (GNB3) polymorphism (CC-genotype) is known to be a risk factor for functional gastrointestinal disorders.

Thus we aimed (1) to characterize the effect of the pro-inflammatory neuropeptide SP on proliferation and (2) Neurokinin 1 receptor (NK1R) expression of peripheral blood mononuclear cells (PBMC) in IBS patients and healthy controls, and (3) evaluate the role of the GNB3 polymorphism in SP mediated responses. Methods: SP induced proliferation and NK1R mRNA expression before and 72 hours after in- vitro SP stimulation of PBMC obtained from 25 (alternating-) IBS patients and matched controls were measured by MTT Assay and reverse transcriptase polymerase chain reaction. Buccal swabs were genotyped for GNB3 polymorphism.

Results: SP caused a dose dependant proliferation of PBMC in controls which was significantly (p<0.05) attenuated in IBS patients. Baseline NK1R mRNA expression was significantly lower (p<0.01) in IBS patients than in healthy subjects. However, compared to baseline, SP stimulation caused a significant increase of NK1 mRNA expression in IBS patients (p<0.01) compared to healthy controls. In healthy subjects CC genotype, but not CT/TT was associated with a significant (p<0.01) decrease of NK1R mRNA expression. In IBS patients, CC genotype was associated with a significantly higher increase than in CT/TT genotype.

Conclusions: IBS patients demonstrate lower proliferation of PBMC’s and altered NK1R expression in response to SP stimulation than healthy subjects suggesting an attenuated immune response which is partly linked to the GNB3 CC genotype.

Keywords: GNB3 polymorphism, Irritable Bowel Syndrome, Substance P, immunologic function