Gastroenterology

Gastroenterology

Volume 116, Issue 1, January 1999, Pages 22-28
Gastroenterology

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

Presented in part at the 1996 annual meeting of the American Gastroenterological Association in San Francisco, California.
https://doi.org/10.1016/S0016-5085(99)70224-6Get rights and content

Abstract

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

Section snippets

Materials and methods

All specimens for this study were obtained from patients treated at our center as part of two randomized, double-blind, controlled trials in patients with treatment-resistant, moderate-to-severe CD. Thirteen patients were treated with infliximab (2 with 5 mg/kg, 7 with 10 mg/kg, and 4 with 20 mg/kg), and 5 were treated with placebo in addition to concomitant medications for CD (corticosteroids in 8 patients, aminosalicylates or sulfasalazine in 11 patients, azathioprine in 6 patients, and

Results

Thirteen patients were treated with infliximab (2 with 5 mg/kg, 7 with 10 mg/kg, 4 with 20 mg/kg), and 5 were treated with placebo. Patient characteristics are shown in Table 1.

. Demographic data

Empty CellInfliximab (n = 13)Placebo (n = 5)
Age (yr)a32.07 (20–47)32.6 (25–41)
Sex (M/F)4/92/3
Disease location
 Colonic61
 Ileocolonic64
 Ileitis20
Baseline CDAIa329 (219–395)290 (230–355)
Concomitant medications for CD
 Sulfasalazine/mesalamine74
 Corticosteroids53
 Azathioprine42
 Antibiotics12
aValues are expressed as means with

Discussion

Therapeutic options for active CD are limited. The advent of anti–TNF-α antibodies created great expectations from their early development. The mechanisms of action of infliximab are still poorly understood. Our study shows that infliximab therapy strongly interferes with the inflammatory process. Reductions of the inflammatory infiltrate are impressive and include complete disappearance of neutrophils as well as an important reduction of mononuclear cells toward normal or even subnormal

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    Supported by a grant from Centocor, Inc., Malvern, Pennslyvania.

    ☆☆

    Address requests for reprints to: Paul J. Rutgeerts, Ph.D., Department of Internal Medicine, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. e-mail: [email protected]; fax: (32) 16-34-44-19.

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