Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept

• Published in: Alimentary pharmacology & therapeutics 2005-02, Vol.21 (3), p.251-258
• Main Authors: Shen, C., Assche, G. V., Colpaert, S., Maerten, P., Geboes, K., Rutgeerts, P., Ceuppens, J. L.
• Format: Article
• Language: English
• Subjects: Adalimumab; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Apoptosis; Biological and medical sciences; Cell Culture Techniques; Cell Membrane - pathology; Depression, Chemical; Digestive system; DNA - analysis; Etanercept; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunoglobulin G - pharmacology; Immunosuppressive Agents - pharmacology; Infliximab; Interleukin-10 - analysis; Interleukin-12 - analysis; Medical sciences; Mitochondria - metabolism; Monocytes - immunology; Monocytes - pathology; Monocytes - ultrastructure; Pharmacology. Drug treatments; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2005.02309.x

Summary Background : Adalimumab, a fully human monoclonal antibody to tumour necrosis factor, was recently introduced for therapy of Crohn's disease. Aim : Since induction of apoptosis of inflammatory cells is thought to be an important mechanism of action of the antitumour necrosis factor monoclonal antibody infliximab, we studied the induction of apoptosis of activated peripheral blood monocytes by adalimumab. Method : Apoptosis was analysed at the levels of the cell membrane, mitochondria and DNA by flow cytometry. Results: We found that both adalimumab and infliximab induced apoptosis in cultured monocytes, while etanercept did not. Apoptosis induction was caspase‐dependent and detectable already after 2 h. The production of interleukin‐10 and interleukin‐12 by monocytes was down‐regulated significantly by adalimumab and infliximab but not by etanercept, while levels of soluble tumour necrosis factor in monocyte cultures were down‐regulated by all three reagents. Conclusions : These data show that both adalimumab and infliximab affect monocyte cytokine production and induce apoptosis of activated monocytes. Our findings will have to be further correlated to therapeutic efficacy of these antitumour necrosis factor reagents.