Serum soluble TNF receptor I and II levels correlate with disease activity in IBD patients

Background: Tumor necrosis factor alpha (TNF alpha) is a proinflammatory cytokine and an important mediator in the pathophysiology of inflammatory bowel disease (IBD). The effects of TNF alpha are mediated by 2 specific receptors, a 55-kDa protein (TNF-RI) and a 75-kDa receptor (TNF-RII), which are usually bound to the cell surface. Soluble TNF receptors I and II (sTNF-RI + II) are released by proteolytic cleavage of the extracellular domains of these receptors. Soluble TNF-Rs act as TNF antagonists and can inhibit TNF alpha-mediated proinflammatory effects. Methods: Levels of sTNF-RI + 11 were measured using commercially available enzyme-linked immunosorbent assays (ELISAs). Serum levels of sTNF-RI + 11 of 76 healthy volunteers were compared to serum levels of 373 clinically well-characterized patients with Crohn's disease (CD) and 118 patients with ulcerative colitis (UC) with different disease activity from the German IBD competence network serum bank. CD patient subgroups were defined according to the Vienna Classification. Results: The serum levels of sTNF-RI were significantly increased in all groups (active, chronic active, and remission) of CD and UC patients compared to healthy controls. sTNF-RII levels were significantly higher in active CD patients compared to UC patients with no overlap of the 95% confidence interval. Significantly higher values of sTNF-RII compared to controls were also observed in CD patients and UC patients in remission. There was no statistically significant difference in sTNF-RI or sTNF-RII levels when patient subgroups were analyzed according to disease behavior or disease localization. Conclusion: sTNF-RI is upregulated in the serum of IBD patients compared to healthy controls and could be used as a marker for disease activity. sTNF-RII levels are significantly more elevated in Serum of active CD patients as compared to UC and could be used as an additional parameter to discriminate both diseases.