Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course

The pleiotropic cytokine leukemia inhibitory factor (LIF) possesses proinflammatory properties in common with tumor necrosis factor (TNF-alpha), interleukine (IL) -1 and -6, such as the induction of acute phase protein synthesis. LIF may have chemotactic activity through the induction of IL-8 production. LIF is produced by normal and tumoral cells and appears to facilitate in vivo rat colon carcinoma cells growth. Inflammatory bowel diseases, ulcerative colitis (UC) in particular, are histologically characterized by the infiltration of the colonic mucosa with activated neutrophils, macrophages and lymphocytes. Cytokines with their inflammatory as well as their regulatory activities may play a role in the perpetuation and possibly the initiation of inflammation in this disease and its local and/or systemic complications. Moreover, colorectal cancer is a late well identified complication in patients with long standing inflammatory bowel disease, UC in particular. Taken together, these results suggest that LIF could be involved in tumorigenic and/or metastatic processes of colorectal cells in UC patients. The aims of the present study was to quantify and to compare the colonic and systemic productions of LIF in UC patients. We showed for the first time in patients with UC, a high local production of LIF well correlated with IL-8 production. We also analyzed the effect of LIF on a human colon carcinoma cell line HT29. We demonstrated that LIF stimulated HT29 cell growth in a dose dependent-manner. These results suggest that LIF may play a critical role in the susceptibility of colonic host cells to tumor growth in patients with UC.