摘要
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 pro- file of sCRs in CD patients and their modulation by infliximab and corticoster oids.Methods: We prospectively examined active CD patients(aCD) treated with eit her 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), C D non-inflamed (n=7), and healthy mucosa(n=8). Levels of tumour necrosis factor α(TNF-α), soluble TNF receptor I (sTNFRI), soluble TNF receptor II (sTNFRII) ,interleukin 1 β(IL-1 β), soluble IL-1 receptor I (sIL-1 RI),soluble IL-1 receptor II (sIL-1 RII), IL-6, soluble IL-6 receptor(sIL-6R), and sgp 130 we re measured using ELISA. Results:Higher levels of sTNFRI (P< 0.05, P< 0.01), sTN FRII (P< 0.01,P< 0.01), sIL-1 RI (P< 0.05, NS), IL-6 (P< 0.01, P< 0.01), and s IL-6R (P< 0.05, NS) were observed in aCD compared with rCD and HS. Interestingl y, sIL-1 RII (P< 0.05, P< 0.01) and sgp 130 (P< 0.01, P< 0.01) were profoundly decreased in aCD compared with rCD and HS, and were negatively correlated with C RP. Deficient production of sIL-1 RII was specific to CD (not observed in ulcer ative colitis), and was further con-firmed at the mucosal level. Infliximab dec reased sTNFRII at one and four weeks (P< 0.05) and enhanced sIL-6R levels at on e week (P< 0.05). Corticosteroids increased sIL-1 RII levels at one week (P< 0. 05). Conclusion: CD is associated with dysregulated production of sCRs. Deficien cy in sIL-1 RII and sgp 130 may be essential to CD pathogenesis. Their replacem ent through the use of fusion proteins could represent future alternative therap eutic strategies for CD.
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 pro- file of sCRs in CD patients and their modulation by infliximab and corticoster oids.Methods: We prospectively examined active CD patients(aCD) treated with eit her 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), C D non-inflamed (n=7), and healthy mucosa(n=8). Levels of tumour necrosis factor α(TNF-α), soluble TNF receptor I (sTNFRI), soluble TNF receptor II (sTNFRII) ,interleukin 1 β(IL-1 β), soluble IL-1 receptor I (sIL-1 RI),soluble IL-1 receptor II (sIL-1 RII), IL-6, soluble IL-6 receptor(sIL-6R), and sgp 130 we re measured using ELISA. Results:Higher levels of sTNFRI (P< 0.05, P< 0.01), sTN FRII (P< 0.01,P< 0.01), sIL-1 RI (P< 0.05, NS), IL-6 (P< 0.01, P< 0.01), and s IL-6R (P< 0.05, NS) were observed in aCD compared with rCD and HS. Interestingl y, sIL-1 RII (P< 0.05, P< 0.01) and sgp 130 (P< 0.01, P< 0.01) were profoundly decreased in aCD compared with rCD and HS, and were negatively correlated with C RP. Deficient production of sIL-1 RII was specific to CD (not observed in ulcer ative colitis), and was further con-firmed at the mucosal level. Infliximab dec reased sTNFRII at one and four weeks (P< 0.05) and enhanced sIL-6R levels at on e week (P< 0.05). Corticosteroids increased sIL-1 RII levels at one week (P< 0. 05). Conclusion: CD is associated with dysregulated production of sCRs. Deficien cy in sIL-1 RII and sgp 130 may be essential to CD pathogenesis. Their replacem ent through the use of fusion proteins could represent future alternative therap eutic strategies for CD.
