Linoleic acid, but not oleic acid, upregulates the production of interleukin-8 by human intestinal smooth muscle cells isolated from patients with Crohnʹs disease

Background & aims: Crohnʹs disease is a chronic inflammatory bowel disease (IBD) of unknown etiology. In this study, we investigated the hypothesis that dietary fatty acids, linoleic acid (LA) and oleic acid (OA), could be involved in the inflammatory response through stimulation of the neutrophil chemokine, IL-8. Methods: Human intestinal smooth muscle (HISM) cells were isolated from normal patients and patients with Crohnʹs disease and cultured for 24 h with LA or OA in the presence or absence of oxidative stress. The concentrations of IL-8 were measured in the media and cellular oxidative stress was quantitated by measurement of thiobarbituric acid reactive substances (TBARSs). Results: Spontaneous production of IL-8 was significantly higher in HISM cells isolated from Crohnʹs bowel compared to control bowel. LA caused a marked, nine-fold, increase in IL-8 secretion by Crohnʹs cells, an effect that could be simulated in normal HISM cells by co-incubation of LA with an oxidizing solution (Ox) composed of hypoxanthine+xanthine oxidase+FeSO4 (OxLA). These effects were inhibited by vitamins C and E. Treatment of Crohnʹs cells with OxLA did not further increase IL-8 over that of LA alone. The effect of LA alone was not associated with an increase in cellular oxidative stress as quantitated by TBARSs. In contrast to the results with LA, treatment with OA or OxOA did not increase IL-8 in either normal or Crohnʹs cells. In addition, OA protected Crohnʹs cells from the increase in TBARSs induced by Ox. In contrast to IL-8, spontaneous production of monocyte chemotactic protein (MCP-1) was significantly lower in Crohnʹs HISM cells as compared to normal cells and exposure to OxLA did not increase its production. Conclusions: LA, but not OA, increased the production of IL-8 by HISM cells. These results suggest that replacement of LA by OA in the diet of Crohnʹs patients and increased intake of a diet rich in antioxidants could be beneficial in decreasing inflammatory activity in Crohnʹs disease.