Cytokine network in chronic perianal Crohn's disease and indeterminate colitis after colectomy

• Published in: Journal of gastrointestinal surgery Vol. 11; no. 1; pp. 16 - 21
• Main Authors: Ruffolo, Cesare, Scarpa, Marco, Faggian, Diego, Romanato, Giovanna, De Pellegrin, AnnaMaria, Filosa, Teresa, Prando, Daniela, Polese, Lino, Scopelliti, Michele, Pilon, Fabio, Ossi, Elena, Frego, Mauro, D'Amico, Davide Francesco, Angriman, Imerio
• Format: Journal Article
• Language: English
• Published: United States 01-01-2007
• Subjects: Adult; Case-Control Studies; Chronic Disease; Colitis - blood; Colitis - surgery; Crohn Disease - blood; Crohn Disease - surgery; Female; Humans; Inflammation Mediators - blood; Interleukin-1 - blood; Interleukin-12 - blood; Interleukin-6 - blood; Male; Middle Aged; Postoperative Complications; Proctocolectomy, Restorative; Statistics, Nonparametric; Tumor Necrosis Factor-alpha - blood
• ISSN: 1091-255X; 1873-4626
• DOI: 10.1007/s11605-006-0021-y

Antitumor necrosis factor alpha (anti-TNF-alpha) therapy in perianal Crohn's disease (CD) is widely established but recent studies suggest that the underlying fistula tract and inflammation may persist. Treatment with a monoclonal antibody against interleukin (IL)-12 was reported to induce clinical responses and remissions in patients with active CD. The aim of our study was to analyze the cytokine network (TNF-alpha, IL-12, IL-1beta, and IL-6) in 12 patients with chronic perianal CD and a Crohn's disease activity index (CDAI) score <150 to exclude active intestinal disease, in 7 patients with indeterminate colitis (IC) after restorative proctocolectomy with perianal complications, in 7 patients with active intestinal CD without perianal manifestations, and in 19 healthy controls. Nonparametric Mann-Whitney U test and Spearman's rank correlation test were used. Serum TNF-alpha levels were significantly higher in patients with IC than perianal CD patients and healthy controls. Serum TNF-alpha levels significantly correlated with perianal CDAI score and with the presence of anal fistulas. Serum IL-12 levels correlated with the presence of anal strictures and were similar in all groups. Serum IL-6 levels were significantly higher in the presence of perianal fistulas and lower in the presence of anal strictures. Our study confirmed that TNF-alpha plays a major role in the perianal and intestinal CD. Furthermore, the significantly higher TNF-alpha serum levels in patients with IC suggest the use of anti-TNF-alpha in such patients. On the contrary, according to our results the efficacy of anti-IL-12 antibodies appears doubtful in chronic perianal CD or IC without anal strictures. The role of IL-6 as a systemic mediator for active chronic inflammation was confirmed and a possible role for its monoclonal antibody was suggested.