Mechanisms Underlying the Effects of Leukocyte Apheresis with a Fiber Filter in a Rat Model of Dextran Sulfate Sodium-Induced Colitis

While several clinical trials have suggested that leukocytapheresis (LCAP) by filtration can benefit patients with active ulcerative colitis, the mechanisms underlying these benefits are largely unknown. The aim of this study was to address the mechanisms that may underlie the therapeutic effects of LCAP using a dextran sulfate sodium-induced colitis model in rats. Treatment with the active column, but not the sham column, improved disease severity by down-regulating pro-inflammatory events, including the cell-proliferative responses and inflammatory cytokine and reactive oxygen production, as well as by up-regulating protective events, including hepatocyte growth factor production, bone marrow-derived endothelial progenitor cell induction, and colonic blood flow levels, which were mediated predominantly by calcitonin gene-related peptide. The improvement was also associated with the increase of Ki-67 labeling in the colonic epithelium. In conclusion, the LCAP procedure was used in a dextran sulfate sodium-induced colitis model in rats under extracorporeal circulation conditions. This approach down-regulated pro-inflammatory events and up-regulated protective events in association with disease improvement. These data suggest that LCAP is feasible in animals and should shed light on the mechanisms of LCAP in clinical settings.