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

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-a, either with neutralizing anti-TNF-alpha binding proteins such as etanercept or via drugs that inhibit de nova TNF-a synthesis like pirfenidone. In the present study, we examined the effects of both classes of drugs on secreted and cell-associated TNF-a produced by THP-1 cells. All of the tested drugs significantly reduced secreted levels of bioactive TNF-a following stimulation with LPS as measured by bioassay. However, etanercept-treated cells had approximately six-fold higher levels of cell-associated TNF-a compared with that of the LPS-alone treatment group. Surprisingly, LPS+infliximab treated cells did not increase cell-associated TNF-a relative to the LPS-alone treatment. Pirfenidone significantly reduced both secreted and cell-associated TNF-a Levels. These drug-related differences in cell-associated TNF-a may have broad implications in the future for the therapeutic uses of anti-TNF-alpha drugs in the management of TNF-a diseases. (c) 2008 Elsevier B.V. All rights reserved.