Received: 03.07.2011 Accepted: 15.09.2011 J Gastrointestin Liver Dis December 2011 Vol. 20 No 4, 365-370 Address for correspondence: Dr. Antonio TURSI, M.D. Gastroenterology Service ASL, BAT, Andria (BT) Italy Email: antotursi@tiscali.it Tumour Necrosis Factor-Alpha Expression in segmental Colitis Associated with Diverticulosis Down-Regulates After Treatment Antonio Tursi 1 , Walter Elisei 2 , Giovanni Brandimarte 3 , Gian Marco Giorgetti 4 , Cosimo Damiano Inchingolo 5 , Rosanna Nenna 5 , Enzo Ierardi 6 1) Gastroenterology Service, ASL BAT, Andria, BT; 2) Division of Gastroenterology, ASL Roma H, Albano Laziale, Rome; 3) Division of Gastroenterology, “Cristo Re” Hospital, Rome; 4) Digestive Endoscopy & Nutrition Unit, “S. Eugenio” Hospital, Rome; 5) Division of Pathology, “Lorenzo Bonomo” Hospital, ASL BAT, Andria (BT); 6) Department of Medical Sciences, Section of Gastroenterology, University of Foggia, Foggia, Italy Abstract Background & Aims : Tumour Necrosis Factor-α (TNF-α) expression may be increased in Segmental Colitis Associated with Diverticulosis (SCAD). Our aim was to assess TNF-α expression in SCAD in relationship to the treatment. methods: 10 patients affected by severe (type B and D) SCAD were studied (6 males, 4 females, mean age 60.54 years, range 43-85 years). All patients were treated with beclomethasone dipropionate 10 mg/day plus a probiotic preparation VSL#3 for 8 weeks. At that time, clinical, endoscopic and histological reassessment was performed. Controls were 5 patients with active ulcerative colitis (UC). Results: After treatment, all SCAD B and no SCAD D patients were in remission. The TNF-α expression dropped from 42.7% (±7.58) to 15.7% (±2.6) in SCAD B patients (p=0.001), and from 40% (±5.9) to 28.6% (±5.3) in SCAD D patients (p=0.005). In UC patients, the TNF-α expression dropped from 45.5% (±5.09) to 22.5% (±2.5) (p=0.001). Neither SCAD B nor SCAD D patients showed a signiicant difference in TNF-α expression compared to UC after treatment. Finally, TNF-α was signiicantly overexpressed in SCAD D than in SCAD B at the end of treatment (p=0.048). Conclusions: TNF-α expression in SCAD down regulates after treatment, and seems to be related to the clinical response to therapy. This behaviour, similar to that of Inlammatory Bowel Diseases (IBD), conirms that this disease should be considered as a subtype of IBD. Key words Segmental colitis – diverticulosis – therapy – ulcerative colitis – tumour necrosis factor α. Introduction Segmental colitis associated with diverticulosis (SCAD) is deined as a chronic colitis that is conined to the diverticular segment in individuals with otherwise uncomplicated diverticular disease [1, 2]. By deinition, the rectum and proximal colon are endoscopically and histologically normal [3]. These inlammatory manifestations differ therefore from conventional colonic diverticulitis, which is essentially a pericolonic inlammatory process that originates within diverticula and extends into the surrounding tissues, but spares the nondiverticular colonic mucosa [4, 5]. Tumour necrosis factor alpha (TNF-α) – a 17-kDa polypeptide produced by macrophages, lymphocytes and natural killer cells – has been shown to play a major role in the inlammatory process, with high levels being found in patients with inlammatory bowel disease (IBD) [6-8]. Although this cytokine has been primarily implicated in the pathogenesis of type 1 helper T (Th1) cell-mediated disorders, such as Crohn‘s disease (CD) and rheumatoid arthritis [9, 10], high levels of TNF-α have also been shown in the blood, stool and intestinal tissues of patients with ulcerative colitis (UC), suggesting a possible role even in type 2 helper T (Th2) cell-mediated diseases [11, 12]. The role of anti-TNF-α drugs (mainly inliximab and adalimumab) in inducing and maintaining a clinical and endoscopic remission in patients with moderate to severe CD and UC has been demonstrated [13-16]. Furthermore, a profound down-regulation of TNF-α in the affected mucosa has been associated with a dramatic improvement, as assessed both histologically and clinically, after inliximab therapy, thereby providing additional support for the importance of this cytokine in IBD pathogenesis [12, 17]. Conversely, only limited data are available regarding the role of TNF-α on SCAD pathogenesis. Some recent studies found an increased expression of TNF-α in patients affected by SCAD [18-20]. Moreover, as in IBD, TNF-α expression in SCAD may correlate with the severity of the disease, suggesting a possible role for TNF-α also in the pathogenesis of SCAD [20, 21]. In light of these patho-physiological hypotheses, and