Leukocyte Apheresis Using a Fiber Filter Suppresses Colonic Injury Through Calcitonin Gene–Related Peptide Induction

Background The aim of this study was to address whether the therapeutic effect of leukocytapheresis (LCAP) depends on calcitonin gene– related peptide (CGRP) induction. Methods An HLA-B27 transgenic rat model was treated with an LCAP column. The effects of LCAP on clinical, endoscopic, and histologic disease activity, the colony-forming ability of colony-forming unit (CFU)–granulocyte macrophages (GMs), colonic blood flow, and tissue expression of tumor necrosis factor (TNF)–α and CGRP were examined. Changes in the effects of LCAP after pretreatment with the CGRP antagonist CGRP8–37 were also observed. A dextran sulfate sodium–induced colitis rat model included treatment with CGRP, and the effect was assessed based on clinical, endoscopic, and histologic disease activity, colonic blood flow, the colony-forming ability of CFU-GMs, and tissue expression of inflammatory cytokines and CGRP receptor families. Results LCAP improved disease activity, enhanced colonic blood flow, and induced the bone marrow colony-forming ability of CFU-GMs with an increase in CGRP mRNA levels. These effects were abolished by pretreatment with CGRP8–37. The administration of CGRP suppressed colitis, promoting colonic blood flow, inducing bone marrow–derived cells, downregulating inflammatory cytokines, and upregulating receptor activity–modifying protein–1. The mRNA and protein levels of inflammatory cytokines in lipopolysaccharide-stimulated mononuclear cells were also decreased after CGRP treatment. Conclusions The therapeutic effects of LCAP depend on CGRP induction. CGRP can effectively suppress colitis through the downregulation of inflammatory events and upregulation of protective events.