Profile of soluble cytokine receptors in Crohn's disease

Introduction: Soluble cytokine receptors (sCRs) modulate the in vivo activity of cytokines. Deficient sCR production could participate in the pathogenesis and course of Crohn's disease ( CD). The aim of the study was to examine the profile of sCRs in CD patients and their modulation by infliximab and corticosteroids. Methods: We prospectively examined active CD patients (aCD) treated with either infliximab (n=21) or corticosteroids (n=9), CD patients in clinical remission (rCD, n=20), ulcerative colitis patients (UC, n=24), and healthy subjects (HS, n=15). Cultures of colonic biopsies were also examined from CD inflamed (n=8), CD non-inflamed (n=7), and healthy mucosa (n=8). Levels of tumour necrosis factor alpha (TNF-alpha), soluble TNF receptor I (sTNFRI), soluble TNF receptor II (sTNFRII), interleukin 1 beta (IL-1 beta), soluble IL-1 receptor I (sIL-1RI), soluble IL-1 receptor II (sIL-1RII), IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 were measured using ELISA. Results: Higher levels of sTNFRI (p<0.05, p<0.01), sTNFRII (p<0.01, p<0.01), sIL-1RI (p<0.05, NS), IL-6 (p<0.01, p<0.01), and sIL-6R (p<0.05, NS) were observed in aCD compared with rCD and HS. Interestingly, sIL-1RII (p<0.05, p<0.01) and sgp130 (p<0.01, p<0.01) were profoundly decreased in aCD compared with rCD and HS, and were negatively correlated with CRP. Deficient production of sIL-1RII was specific to CD ( not observed in ulcerative colitis), and was further confirmed at the mucosal level. Infliximab decreased sTNFRII at one and four weeks (p<0.05) and enhanced sIL-6R levels at one week (p<0.05). Corticosteroids increased sIL-1RII levels at one week (p<0.05). Conclusion: CD is associated with dysregulated production of sCRs. Deficiency in sIL-1RII and sgp130 may be essential to CD pathogenesis. Their replacement through the use of fusion proteins could represent future alternative therapeutic strategies for CD.