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P189. Fatigue in IBD patients is associated with differences in immune parameters


C. de Haar1, L. Vogelaar1, B. Aerts1, M.P. Peppelenbosch2, E. Kuipers3, C.J. van der Woude4

1Erasmus Medical Center, Gastroenterology and Hepatology, Rotterdam, Netherlands; 2Erasmus Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, Netherlands; 3Erasmus Medical Center, Rotterdam, Netherlands; 4Erasmus Medical Center, Department of Gastroenterology & Hepatology, Rotterdam, Netherlands



Background: Fatigue contributes to the decreased quality of life of inflammatory bowel disease (IBD) patients. The immune system plays an important role in various cases of disease-associated fatigue. As such, we were interested whether there are detectable differences in immune parameters between fatigue and non-fatigue IBD patients. In this study only patients in clinical and biological remission were included to rule out inflammation-associated fatigue.

Methods: After informed consent 78 IBD patients in clinical and biological remission, defined by a normal Harvey–Bradshaw Index (<5) and Colitis activity index (<10), normal levels of hemoglobin, iron, CRP, liver enzymes and normal kidney function were included. All patients were phenotyped according to the Montreal classification and the Checklist Individual Strength (CIS) was used to assess fatigue. Other parameters included were: Quality of life scores and medication use.

We used flow cytometry on peripheral blood samples to investigate the differences in leukocyte subsets. Furthermore, serum levels of IL‑4, IL‑5, IL‑6, IL‑8, IL‑10, IL‑12, TNF‑α and IFN-γ were measured using ELISA.

Results: In total 54 fatigue patients (CIS score of ≥35) and 24 patients without fatigue were included. Significantly more females were included in the fatigue (F) group compared to the non-fatigue (NF) group (69% vs. 46%; p = 0.032). The other characteristics revealed no significant differences between the groups.

Flow cytometry data showed a significant lower percentage of monocytes (5% vs. 7%; p = 0.010), higher percentage of memory T‑cells (42% vs. 34%; p = 0.006) and higher percentage of neutrophils (75% vs. 68%; p = 0.043) in fatigue patients compared to non-fatigue patients.

Mean serum levels of IL‑5 (F: 57 pg/ml, NF: 2 pg/ml; p = 0.021) and IL‑12 (F: 9 pg/ml, NF: 3 pg/ml; p = 0.003) were significantly higher in fatigue patients while IL‑8 (F: 10 pg/ml, NF: 61 pg/ml; p = 0.012) was significantly lower in fatigue patients compared to non-fatigue patients. No other significant differences were seen in cytokines or leukocyte subsets.

Conclusions: This study shows for the first time that there are immunological differences between fatigue and non-fatigue IBD patients in remission. The immune stimulation in fatigue could represent an on-going infection or autoimmune response that occurs without any clinical or histological signs of IBD. Further exploration of the underlying factors may uncover therapeutic targets for the treatment of fatigue in IBD patients.