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

• Published in: International immunopharmacology Vol. 8; no. 5; pp. 679 - 687
• Main Authors: Grattendick, K.J., Nakashima, J.M., Feng, L., Giri, S.N., Margolin, S.B.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.05.2008; Elsevier
• Subjects: Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antibodies, Monoclonal - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Cell Survival - drug effects; Culture Media; Cytokines; Enzyme-Linked Immunosorbent Assay; Etanercept; Humans; Immunoglobulin G - pharmacology; Immunohistochemistry; Infliximab; Lipopolysaccharides - pharmacology; Medical sciences; Pharmacology. Drug treatments; Pirfenidone; Pyridones - pharmacology; Receptors, Tumor Necrosis Factor; Tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - biosynthesis; Tumor necrosis factor-alpha; Etanercept; Infliximab; Cytokines; Pirfenidone; Drug; Cytokine; Monoclonal antibody; Anti-Tumor Necrosis Factor-alpha; In vitro; Immunomodulator; Anticytokine; Antagonist; Immunosuppressive agent; Fusion protein; Tumor necrosis factor α; Release
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2008.01.013

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