Inhibition of Inflammatory Cytokines and Induction of Myeloid-Derived Suppressor Cells by the Effects of Granulocyte and Monocyte Adsorption Apheresis

Ther Apher Dial. 2017 Dec;21(6):628-634. doi: 10.1111/1744-9987.12580. Epub 2017 Sep 22.

Abstract

Pro-inflammatory cytokines are involved in the pathogenesis of inflammatory skin diseases attributable to activated neutrophils and macrophages. Myeloid-derived suppressor cells (MDSCs) play an important role in the regulation of the immune response and possess strong immunosuppressive and anti-inflammatory properties. Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument featuring columns containing cellulose acetate (CA) beads, is designed to remove pathogenic myeloid lineage cells. The purpose of this study was to investigate the effects of GMA on cytokine production and MDSC induction. The serum level of various inflammatory cytokines and the incidence of MDSCs in peripheral blood before and after GMA treatment were recorded. Cytokines were assayed with the suspension-array method in 38 patients. The incidence of MDSCs was analyzed by FACS in eight patients and the effect of GMA on in vitro MDSC induction was examined using a mini-column system that mimics GMA. The serum level of IL-2Rα (P = 0.030), IL-8 (P = 0.018), and MIF (P = 0.0002) was significantly decreased by GMA and the incidence of MDSCs was increased (P = 0.030). With the mini-column system, MDSCs were induced in the peripheral blood of five healthy volunteers; the in vitro induction was significantly inhibited by inactivation of the complement component iC3b. The clinical effectiveness of GMA may be attributable to the inhibition of pro-inflammatory cytokines and the induction of anti-inflammatory MDSCs by iC3b activation via the CA beads in the GMA column.

Keywords: Cytokine; Granulocyte and monocyte adsorption apheresis; Myeloid-derived suppressor cells; Neutrophilic dermatosis; iC3b.

MeSH terms

  • Adsorption
  • Cellulose / analogs & derivatives
  • Cellulose / chemistry
  • Complement C3b / metabolism
  • Cytokines / blood*
  • Granulocytes / metabolism
  • Humans
  • Inflammation Mediators / blood
  • Leukapheresis / methods*
  • Monocytes / metabolism
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Skin Diseases / pathology
  • Skin Diseases / therapy*

Substances

  • Cytokines
  • Inflammation Mediators
  • acetylcellulose
  • Complement C3b
  • Cellulose