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

Abstract

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.