Infliximab induces apoptosis of monocytes and T lymphocytes in a human-mouse chimeric model

Tumor necrosis factor (TNF) antagonism with monoclonal antibodies is an effective therapy for severe Crohn's disease and rheumatoid arthritis. Recent studies have suggested that induction of apoptosis of inflammatory cells contributes to this therapeutic effect. We investigated whether inflixim...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 115(2005), 3 vom: 31. Juni, Seite 250-9
1. Verfasser: Shen, Chong (VerfasserIn)
Weitere Verfasser: Maerten, Philippe, Geboes, Karel, Van Assche, Gert, Rutgeerts, Paul, Ceuppens, Jan L
Format: Aufsatz
Sprache:English
Veröffentlicht: 2005
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Antibodies, Monoclonal Immunoglobulin G Receptors, IgG Receptors, Tumor Necrosis Factor Infliximab B72HH48FLU Etanercept OP401G7OJC
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245 1 0 |a Infliximab induces apoptosis of monocytes and T lymphocytes in a human-mouse chimeric model 
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520 |a Tumor necrosis factor (TNF) antagonism with monoclonal antibodies is an effective therapy for severe Crohn's disease and rheumatoid arthritis. Recent studies have suggested that induction of apoptosis of inflammatory cells contributes to this therapeutic effect. We investigated whether infliximab (a mouse-human IgG1 chimeric anti-TNF monoclonal antibody) could induce apoptosis in vivo in human-mouse chimeras, created by reconstitution of severe combined immunodeficiency/beige mice with THP-1 (human monocytic cell line) or Jurkat cells (human T cell line). Infliximab treatment of chimeric mice depleted spleen and peritoneum from THP-1 cells and Jurkat cells and decreased production of the human cytokines IL-10 and IL-12 in vivo. Cell death was shown to occur already within 1 h of treatment. Infliximab effects were independent of FcgammaR binding or complement activation. Cell death resulted from apoptosis induction in a caspase-dependent pathway, as evidenced by the in vitro protective effect of the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyketone (Z-VAD-FMK). These data provide support for caspase-dependent apoptosis induction being the mechanism of action of infliximab in vivo 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
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650 7 |a Immunoglobulin G  |2 NLM 
650 7 |a Receptors, IgG  |2 NLM 
650 7 |a Receptors, Tumor Necrosis Factor  |2 NLM 
650 7 |a Infliximab  |2 NLM 
650 7 |a B72HH48FLU  |2 NLM 
650 7 |a Etanercept  |2 NLM 
650 7 |a OP401G7OJC  |2 NLM 
700 1 |a Maerten, Philippe  |e verfasserin  |4 aut 
700 1 |a Geboes, Karel  |e verfasserin  |4 aut 
700 1 |a Van Assche, Gert  |e verfasserin  |4 aut 
700 1 |a Rutgeerts, Paul  |e verfasserin  |4 aut 
700 1 |a Ceuppens, Jan L  |e verfasserin  |4 aut 
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