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

FJ Baert, GR D'Haens, M Peeters, MI Hiele… - Gastroenterology, 1999 - Elsevier
FJ Baert, GR D'Haens, M Peeters, MI Hiele, TF Schaible, D Shealy, K Geboes, PJ Rutgeerts
Gastroenterology, 1999Elsevier
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 …
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. GASTROENTEROLOGY 1999;116:22-28
Elsevier