Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept.
BACKGROUND
Adalimumab, a fully human monoclonal antibody to tumour necrosis factor, was recently introduced for therapy of Crohn's disease.


OBJECTIVE
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.


METHODS
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.
Shen
C
C
Laboratory of Experimental Immunology, Catholic University, Leuven, Belgium.
Assche
G V
GV
Colpaert
S
S
Maerten
P
P
Geboes
K
K
Rutgeerts
P
P
Ceuppens
J L
JL
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000473:pathology; D004247:DNA / Q000032:analysis; D003864:Depression, Chemical; D000068800:Etanercept; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D000069285:Infliximab; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000473:pathology* / Q000648:ultrastructure; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D004247:DNA; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept