Clinical Response Is Associated with Elevated Plasma Interleukin-1 Receptor Antagonist During Selective Granulocyte and Monocyte Apheresis in Patients with Ulcerative Colitis

Abstract

Depletion of granulocytes and monocytes (GM) by selective apheresis (GMA) with an Adacolumn exerts an anti-inflammatory effect in patients with ulcerative colitis (UC) or rheumatoid arthritis. However, the mechanism of the anti-inflammatory effect of GMA is not fully understood yet. We investigated the effect of GMA on the plasma concentration of interleukin-1 receptor antagonist (IL-1ra), a potent anti-inflammatory cytokine. Twenty-six patients with active UC received GMA at one session per week for 5 consecutive weeks. Clinical response was defined as Deltaclinical activity index (DeltaCAI=CAI at entry - CAI at post)>or=4, while clinical remission was defined as CAI<or=4. Twenty-one of twenty-six patients (80.8%) responded to GMA. In the first session, plasma from responder patients showed a significant (P < 0.01) increase in IL-1ra in the Adacolumn outflow. In contrast, there was no change in IL-1ra in nonresponders. In conclusion, release of IL-1ra during GMA might be one mechanism of clinical efficacy associated with this therapy.

Long-term follow-up with Granulocyte and Monocyte Apheresis re-treatment in patients with chronically active inflammatory bowel disease

“…Further, 26 patients (65%) remained in clinical as well as endoscopic remission for an average of 14 months, ranging from two to 58 months. These remission values (65%) are in line with other studies, however with more homogenous patient selection [45,50]. All 26 patients remained steroid-free during the follow-up period.…”

Release of Interleukin‐1 Receptor Antagonist by Combining a Leukocyte Adsorption Carrier With Ulinastatin

“…In the present study we found that ulinastatin did not inhibit GM adsorption to cellulose acetate beads, and that 10 000 units/mL of ulinastatin augmented the release of IL‐1ra induced by GM adsorption. Ulinastatin and cellulose acetate beads are separately used for patients with ulcerative colitis, and IL‐1ra release is correlated with clinical efficacy (15,17); thus, the present study demonstrates the feasibility of combination therapy with ulinastatin and GMA.…”

Adsorptive Depletion of α4 Integrinhi- and CX3CR1hi-Expressing Proinflammatory Monocytes in Patients with Ulcerative Colitis

“…Other investigators have reported elevated blood levels of antiinflammatory substances including IL-1 receptor antagonist (IL-1ra), IL-10, soluble TNF-a receptors I and II, CD10 -granulocytes, TLR2 low granulocytes, CD25 hi CD4 ? regulatory T cells, and reduced circulating dendritic cells following GMA [15][16][17][18][19][20][21][22][23][24]. These observations have broadened the actions of GMA.…”