Profile of soluble cytokine receptors in Crohn's disease.
BACKGROUND
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 1beta (IL-1beta), 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).


CONCLUSIONS
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.
Gustot
T
T
Division of Gastroenterology, Erasme University Hospital, Free University of Brussels, 808 Lennik St, 1070 Brussels, Belgium. tgustot@ulb.ac.be
Lemmers
A
A
Louis
E
E
Nicaise
C
C
Quertinmont
E
E
Belaiche
J
J
Roland
S
S
Van Gossum
A
A
Devière
J
J
Franchimont
D
D
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D050822:Cytokine Receptor gp130; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D018928:Immunity, Mucosal; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D011446:Prospective Studies; D018121:Receptors, Cytokine / Q000097:blood* / Q000378:metabolism; D012074:Remission Induction; D012995:Solubility; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D005765:Gastrointestinal Agents; C494199:IL6ST protein, human; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha; D050822:Cytokine Receptor gp130; D002097:C-Reactive Protein; D000069285:Infliximab