Background: Interleukin (IL)-17 is a pleiotropic cytokine which acts on both immune and non-immune cells and is over-expressed in a number of inflammatory disorders, including ulcerative colitis (UC). Treatment with Oleuropein (OLE), the major phenolic secoiridoid of olive tree leaves, has been found to inhibit Th17 response in a DSS-induced mouse model of colitis, but no data exist in UC patients. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with UC.
Methods: Biopsies obtained during colonoscopy from 14 patients with active UC (8 M, 39–80 years, median 59; Mayo score 4–9, median 6) were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 μg/mL in the presence or absence of 3mM OLE for 20 h. Levels of IL-17 were assessed in total protein extracts and culture supernatant from treated colonic biopsies, by Western blotting and ELISA, respectively. A microscopic evaluation of the cultured biopsies was performed by staining with hematoxylin and eosin and immunohistochemistry for CD3, CD4, CD20, CD68 (Novus Biological, Milan, Italy). Data were analysed using the Mann–Whitney U test. A level of p<0.05 was considered statistically significant.
Results: Levels of IL-17 were significantly lower in samples treated with OLE+EC-LPS when compared with those treated with EC-LPS alone, both in colonic mucosal biopsies (0.71±0.08 a.u. vs 1.26±0.42 a.u., p=0.03) and culture supernatant (21.16±8.64 pg/ml vs 40.67±9.24 pg/ml, p=0.01). On histologic evaluation, the presence of OLE reduced lymphocytes T CD3 and T helper CD4 in the submucosa and in the lamina propria; decreased the magnitude of the lymphoid aggregates B type CD20 limiting them in the submucosa as inflammatory residues, attenuates in the inflammatory process with lesser infiltration of leukocytes, mainly mononuclear cells, and increased CD68 histiocytes preserving mucin secretion and restoring goblet cells in the superficial portion of the glands.
Conclusions: In this study we found that OLE downregulates IL-17 production in organ culture of colonic biopsies from UC patients and attenuates the inflammatory damage. This provides new data supporting a potential role for this nutraceutical compound in the treatment of UC.