Correlation of serum soluble TNF-alpha receptors I and II levels with disease activity in patients with ulcerative colitis

Abstract

Objectives: TNF-alpha has a major role in inflammatory bowel disease via two receptors, p55 (RI) and p75 (RII) expressed on many cell types, in particular neutrophils and monocytes (GM). Upon activation of these leukocytes, RI and RII are shed into the medium and can neutralize TNF. Accordingly, soluble RI and RII (s-RI/RII) are believed to have potent antiinflammatory actions. Further, in active UC, GM are elevated with activation behavior and recently adsorptive GM apheresis (GMA) in patients with severe UC was associated with a dramatic efficacy. In this study, we investigated the effects of GMA on serum s-RI/RII.

Methods: Thirty-one patients with UC, clinical activity index (CAI) 11.1 were treated with GMA by using the Adacolumn. In the column, leukocytes which bear the FcgammaR and complement receptors adhere to the column apheresis carriers (neutrophils, monocytes, and a small fraction of lymphocytes). One GMA session was 60 min at 30 mL/min and each patient could receive up to 11 sessions over 8 wk. Serum s-RI/II were measured in the blood at the column inflow (peripheral blood, time 0 and 60 min) and outflow at 60 min.

Results: Serum s-RI/RII showed strong correlation with CAI, r = 0.849 (p < 0.001) and r = 0.867 (p < 0.001), respectively and were greater than when patients were in remission or the levels in controls (p < 0.001). s-RI/RII at the column outflow were higher compared with inflow (p < 0.05) suggesting that RI/RII were shed from leukocytes which adhere to the carriers. Similarly s-RI/RII were significantly increased in the peripheral blood at the end of the 60 min GMA session compared with time 0. After 11 GMA sessions, CAI fell to remission level in 26 of 31 patients accompanied by falls of s-RI/RII.

Conclusions: The sources of s-RI/RII are believed to be activated monocytes and neutrophils with further release when these leukocytes adhere to the column carriers. s-RI/RII released during GMA should contribute to the clinical efficacy of this procedure.