Cytokine network in chronic perianal Crohn's disease and indeterminate colitis after colectomy.
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.
Ruffolo
Cesare
C
Clinica Chirurgica, Department of Surgical and Gastroenterological Sciences, University of Padua, Padova, Italy. cruffolo@hotmail.com
Scarpa
Marco
M
Faggian
Diego
D
Romanato
Giovanna
G
De Pellegrin
AnnaMaria
A
Filosa
Teresa
T
Prando
Daniela
D
Polese
Lino
L
Scopelliti
Michele
M
Pilon
Fabio
F
Ossi
Elena
E
Frego
Mauro
M
D'Amico
Davide Francesco
DF
Angriman
Imerio
I
D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D003092:Colitis / Q000097:blood* / Q000601:surgery*; D003424:Crohn Disease / Q000097:blood* / Q000601:surgery*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D016737:Proctocolectomy, Restorative; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12