The link between meal related symptoms and cytokine release in patients with functional dyspepsia

Aims: Immune responses are believed to play a critical role for the manifestation of functional gastrointestinal disorders. In recent studies we have demonstrated (AJG 2004;99(4):703–10) differences in systemic cytokine levels after a meal. The current study aimed to assess the link between baseline and lipopolysacharide (LPS) stimulated cytokine levels and the symptom pattern in patients with functional dyspepsia.

Methods: 22 (H. pylori-negative) patients with functional dyspepsia according to ROME II (8 males, aged 21–72 mean 46.3) were recruited after a standardized diagnostic work-up. Symptom pattern and severity of symptoms were assessed utilizing the BDQ (Bowel Disease Questionnaire). Peripheral blood mononuclear cells (PBMC) from 40 cc whole blood were freshly isolated by density gradient centrifugation and cultured for 24 hours in RPMI 1640 supplemented with 10% FCS. Basal and E. coli LPS (1–100ng/ml) stimulated pro-inflammatory cytokine production (TNF-a, IL-1b, IL-6) of PBMC was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Overall, intensity of abdominal pain or discomfort were significantly associated with baseline TNF-α (r=0.70, p<0.001), IL-1β (r=0.54, p<0.001) and IL-6 (r=0.51, p<0.002). The release of TNF-α, IL-1β and IL-6 were significantly higher in patients reporting early satiety and meal related pain (TNF-α p<0.001; IL-1 β p<0.01; IL-6 p<0.05) compared to patients without these symptoms. Cytokine release was not linked to nausea or vomiting. Summary and

Conclusion: In-vitro-release of cytokines from PBMC is linked to severity of symptoms and in particular associated with meal related complaints. Based upon these data we conclude that immune responses mediated by cytokine release are linked to the symptom pattern in patients with functional dyspepsia.