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* = Presenting author

P073 The role of eicosanoids in Inflammatory Bowel Disease

U. Pisano1, D. Hildebrand1, B. Maskrey2, P. Whitfield2, A. Watson*1

1NHS Highlands, General Surgery, Raigmore Hospital, Inverness, United Kingdom, 2University of the Highlands and Islands, Lipidomics Research Facility, Inverness, United Kingdom

Background

Inflammatory molecules from the class of eicosanoids, in particular prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), are associated with more severe forms of Inflammatory Bowel Disease (IBD) and in contrast, prostaglandin D2 (PGD2) and lipoxin A4 (LXA4) have been described in increased quantity during disease remission.

Methods

A metabolomic analysis of longitudinal samples of serum collected over 2 years from 30 patients affected by UC and CD. The presence of eicosanoids was evaluated with tandem HPLC - MS (High Performance Liquid Chromatography - Mass Spectrometry) and correlated with clinical indices of activity, the Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw Index (HBI). Quantitative variables were analyzed using a Spearman's correlation coefficient; difference in distribution between dichotomous variables was sought with the Mann-Whitney U test.

Results

There was no correlation between the pro-inflammatory eicosanoid LTB4 and clinical activity (Spearman's rho -0.17, p=0.36). Median concentration levels of PGE2 did correlate with activity scores (Spearman's rho, 0.457; p=0.01). A negative correlation between PGD2 and clinical activity could not be demonstrated (Spearman' rho 0.035, p=0.85). LXA4, despite being expected to be associated with disease remission, featured an almost significant correlation coefficient of 0.39 (p=0.07). LXA4 was increased in patients receiving anti-TNF therapy (Mann-Whitney, p=0.044), who also had a more severe clinical activity score (p=0.081).

Conclusion

Although certain eicosanoids have been shown to reflect disease activity when isolated from intestinal biopsies and serum, to our knowledge a longitudinal study that evaluates different eicosanoids using state of the art HPLC-MS represents a novel approach. While a recent study reported the lipoxin concentration to be immeasurable in healthy volunteers, we successfully isolated LXA4 in half of our samples, from patients with more severe disease.

This experimental pilot study constitutes the basis for a successive pragmatic assessment of the role of eicosanoids in IBD: patients seen with worsening symptoms in secondary and tertiary care will be prospectively recruited for clinical and biological data collection before medical and surgical therapy. Variation of PGE2 and LXA4 concentration will be used to predict disease severity and identify patterns of remission.