Effects of three anti-TNF-alpha drugs: etanercept, infliximab and pirfenidone on release of TNF-alpha in medium and TNF-alpha associated with the cell in vitro

Int Immunopharmacol. 2008 May;8(5):679-87. doi: 10.1016/j.intimp.2008.01.013. Epub 2008 Feb 11.


Tumor necrosis factor-alpha (TNF-alpha) is a vital component of the inflammatory process and its aberrant over-expression has been linked to numerous disease states. New treatment strategies have sought to reduce circulating TNF-alpha, either with neutralizing anti-TNF-alpha binding proteins such as etanercept or via drugs that inhibit de novo TNF-alpha synthesis like pirfenidone. In the present study, we examined the effects of both classes of drugs on secreted and cell-associated TNF-alpha produced by THP-1 cells. All of the tested drugs significantly reduced secreted levels of bioactive TNF-alpha following stimulation with LPS as measured by bioassay. However, etanercept-treated cells had approximately six-fold higher levels of cell-associated TNF-alpha compared with that of the LPS-alone treatment group. Surprisingly, LPS+infliximab treated cells did not increase cell-associated TNF-alpha relative to the LPS-alone treatment. Pirfenidone significantly reduced both secreted and cell-associated TNF-alpha levels. These drug-related differences in cell-associated TNF-alpha may have broad implications in the future for the therapeutic uses of anti-TNF-alpha drugs in the management of TNF-alpha diseases.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antibodies, Monoclonal / pharmacology*
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Culture Media
  • Enzyme-Linked Immunosorbent Assay
  • Etanercept
  • Humans
  • Immunoglobulin G / pharmacology*
  • Immunohistochemistry
  • Infliximab
  • Lipopolysaccharides / pharmacology
  • Pyridones / pharmacology*
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Culture Media
  • Immunoglobulin G
  • Lipopolysaccharides
  • Pyridones
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • pirfenidone
  • Etanercept