Increased lymphatic vessel density and lymphangiogenesis in inflammatory bowel disease

Background Involvement of the lymphatic system in inflammatory bowel disease (IBD) has been suggested. Aims To examine the density and distribution of lymphatic vessels (LV) within inflamed and non-inflamed wall sections of IBD patients compared with controls, and to evaluate expression of major lymphangiogenic factors. Methods Ileal and colon specimens of 22 patients with Crohn's disease (CD), 16 patients with ulcerative colitis (UC) and 11 controls were studied. Quantification of LV was performed using immunohistochemistry with podoplanin and D2-40 antibodies on seven randomly selected fields. Mucosal expression of podoplanin and lymphangiogenic factor mRNA was measured using PCR. Results In CD patients, lymphatic density was significantly increased in non-inflamed and inflamed ileal (P < 0.01 and P < 0.001) and colonic (P < 0.01 and P < 0.001) mucosa compared to controls. Podoplanin mRNA levels were similar in non-inflamed mucosal areas and controls, whereas a four- and sixfold increase was seen in inflamed ileal and colonic areas (P < 0.05). In UC, lymphatic density increased fourfold in non-inflamed (P < 0.001) and fivefold in inflamed colonic mucosa (P < 0.001) compared with controls. An increase in podoplanin mRNA levels was seen in both non-inflamed and inflamed areas (P < 0.01) compared with controls. In CD and UC, lymphatics were found throughout the inflamed mucosa, including the upper half of the lamina propria. Expression of lymphangiogenic factors was similar in patients and controls. Conclusions Increased density of lymphatic vessels is a constant feature of IBD and is present in non-inflamed areas. It is transmural in CD and confined to the mucosa in UC. Its origin remains unclear.