Serum Polyunsaturated Fatty Acids Correlate with Serum Cytokines and Clinical Disease Activity in Crohn's Disease

Abstract

Crohn's disease (CD) has been associated with an increased consumption of n-6 polyunsaturated fatty acid (PUFA), while greater intake of n-3 PUFA has been associated with a reduced risk. We sought to investigate serum fatty acid composition in CD, and associations of fatty acids with disease activity, cytokines, and adipokines. Serum was prospectively collected from 116 CD subjects and 27 non-IBD controls. Clinical disease activity was assessed by the Harvey Bradshaw Index (HBI). Serum fatty acids were measured by gas chromatography. Serum cytokines and adipokines were measured by Luminex assay. Dietary histories were obtained from a subset of patients. Nine serum cytokines and adipokines were increased in CD versus controls. CD subjects had increased percentage serum monounsaturated fatty acids (MUFA), dihomo-gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and oleic acid, but decreased arachidonic acid (AA) versus controls. The % total n-3 fatty acids and % EPA directly correlated with pro-inflammatory cytokine levels and HBI, whereas the % total n-6 fatty acids were inversely correlated with pro-inflammatory cytokine levels and HBI. CD subjects had increased caloric intake versus controls, but no alterations in total fat or PUFA intake. We found differences in serum fatty acids, most notably PUFA, in CD that correlated both with clinical disease activity and inflammatory cytokines. Our findings indicate that altered fatty acid metabolism or utilization is present in CD and is related to disease activity.

Figure 1

Clinical disease activity correlates with serum fatty acids. Clinical disease activity correlates directly with (a) total phospholipids, % MUFA, % n-3, % EPA, (EPA + DHA)/AA ratio, and n-3/n-6 ratio, but inversely correlates with (b) % n-6 and linoleic acid. Clinical disease activity by HBI shown as a continuous variable on the Y-axis. The spearman rho (R) is shown with corresponding p-value. The solid line represents the line of best fit with 95% confidence intervals (dashed lines). n = 111 for CD patients.

Figure 2

Serum % n-3 fatty acids directly correlate with serum pro-inflammatory cytokines. Serum % n-3 (a) correlates directly to CCL11, IL-17A, IFN-γ, G-CSF, IL-5, and MIP-1α. Serum % EPA (b) correlates directly to CCL11, IL-7, IFN-γ, G-CSF, and MIP-1α. The Spearman rho (R) is shown with the corresponding p-value. The solid line represents the line of best fit with 95% confidence intervals (dashed lines). Serum % n-3 did not correlate with any cytokines/adipokines in controls. n = 114 for CD patients.

Figure 3

Serum % n-6 inversely correlates with serum pro-inflammatory cytokines. Serum % n-6 inversely correlates with G-CSF, IL-8, TNF-α, and resistin. The Spearman rho (R) is shown with the corresponding p-value. The solid line represents the line of best fit with 95% confidence intervals (dashed lines). Serum % n-6 did not correlate with any cytokines/adipokines in controls. n = 114 for CD patients.