Immunoregulatory Effects of Adsorptive Granulocyte and Monocyte Apheresis in Patients with Drug Refractory Crohn's Disease

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn's disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function. Thirteen CD patients were treated with a single GMA session. The mean CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years, respectively. Eight healthy volunteers participated as a control group. From CD patients, whole blood was taken immediately before and after the GMA session directly from the GMA column inflow and outflow lines. Broad spectrum serum key cytokines and chemokines were measured by suspension-array and ELISA. At baseline, almost all assayed inflammatory cytokines were significantly elevated in CD patients. Treg-associated cytokines including IL-10 (P < 0.02) and transforming growth factor (TGF)-beta 1 (P < 0.03), were higher in the GMA column outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-gamma/IL-10 was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10 (P < 0.02) because an elevation of pro-inflammatory IFN-gamma (Th1) was not observed at the GMA column outflow. A single GMA session had a significant impact on the Treg profile. Treg-related cytokines like IL-10 and TGF-beta 1 in the blood returning to the patients from the GMA column outflow were elevated, while pro-inflammatory cytokines like IFN-gamma were not. This action of GMA is potentially very interesting in patients with immune disorders, like CD patients.