Effects of etanercept are distinct from infliximab in modulating proinflammatory genes in activated human leukocytes.
Proinflammatory diseases like rheumatoid arthritis, Crohn's disease, and psoriasis have been treated by the tumor necrosis factor (TNF) antagonists infliximab and etanercept with different degrees of success. Although these agents are widely used in humans, little is known about their mechanisms of action or why etanercept and infliximab have differences in clinical activity. In this study, we define leukocyte genes that are suppressed by etanercept within 24 hours of exposure. Compared to previous work with infliximab, fewer immune-related genes are suppressed by etanercept. Importantly, the range of genes suppressed by these alternative TNF inhibitors is only partially overlapping, suggesting each has unique immune modulating effects. In sharp contrast to etanercept, infliximab strongly suppresses genes associated with "Type 1" immune responses (IFN-gamma and the IL-12-receptor beta 2 subunit), providing a clear mechanism for clinically relevant immune suppression.
Haider
Asifa S
AS
Laboratory of Investigative Dermatology, Rockefeller University, New York, New York 10021, USA.
Cardinale
Irma R
IR
Whynot
Julia A
JA
Krueger
James G
JG
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D000069285:Infliximab; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D007074:Immunoglobulin G; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept