Tumor necrosis factor α antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis

Background & Aims:Anti–tumor necrosis factor α monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. Methods:Thirteen patients with steroid-refractory Crohn's disease were treated with a single infusion of infliximab (5–20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor α, intercellular adhesion molecule 1, lymphocyte function–associated antigen, CD4, CD8, and interleukin 4 were performed. Results:Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4+and CD8+T lymphocytes and CD68+monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function–associated antigen 1–expressing and interleukin 4– and tumor necrosis factor–positive lamina propria mononuclear cells sharply decreased. Conclusions:Infliximab dramatically decreases histological disease activity in Crohn's ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators.