Tumour necrosis factor alpha down-regulation parallels inflammatory regression in ulcerative colitis patients treated with infliximab

BackgroundTreatment with the anti-tumour necrosis factor α monoclonal antibody infliximab has been shown to be effective in moderate-to-severe ulcerative colitis. However, its effect on the mucosal histopathological abnormalities of this disease is largely unknown. This study aimed to assess the immunohistological effect of infliximab in ulcerative colitis.MethodsNine patients with moderate-to-severe ulcerative colitis received infliximab (5 mg/kg) at weeks 0, 2 and 6, respectively. Colonic biopsies were collected before therapy and at week 10, when the Mayo score (including the endoscopic subscore) was also assessed. Severity of inflammation was evaluated by histologic score and histomorphometry. Immunohistochemical staining with antibody against tumour necrosis factor α was performed on all biopsies and expressed as percentage of positive stromal cells/1000 counted (tumour necrosis factor α score).ResultsA profound down-regulation of mucosal tumour necrosis factor α occurred in all the six patients who achieved a clinical response, but not in the three who did not respond. Median tumour necrosis factor α score dropped from 44.8 (range 35–58.3) to 12.8 (range 5.3–15.3) in the responders (p = 0.03), whilst it remained unchanged in the non-responders. Such effect was related with a dramatic regression of the median histologic score, which dropped from 2.7 (range 2–3) to 0.5 (range 0.0–1.5) in responder patients (p = 0.002). This was related to a virtual disappearance of neutrophils in responders (r = 0.72; p = 0.002; Spearman's test), but not in those who did not improve. Tumour necrosis factor α score appeared to be correlated with the histologic, endoscopic and clinical activity.ConclusionsA profound tumour necrosis factor α down-regulation appears to be strictly associated with a dramatic regression of the inflammation in patients with moderate-to-severe ulcerative colitis treated with infliximab. Such immunohistochemical effect seems to be critical for a clinical and endoscopic response to therapy.