PMID- 18387510 OWN - NLM STAT- MEDLINE DCOM- 20080722 LR - 20220321 IS - 1567-5769 (Print) IS - 1567-5769 (Linking) VI - 8 IP - 5 DP - 2008 May TI - 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. PG - 679-87 LID - 10.1016/j.intimp.2008.01.013 [doi] AB - 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. FAU - Grattendick, K J AU - Grattendick KJ AD - Solanan, Inc., Dallas, TX 75229, USA. FAU - Nakashima, J M AU - Nakashima JM FAU - Feng, L AU - Feng L FAU - Giri, S N AU - Giri SN FAU - Margolin, S B AU - Margolin SB LA - eng PT - Journal Article DEP - 20080211 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Antibodies, Monoclonal) RN - 0 (Culture Media) RN - 0 (Immunoglobulin G) RN - 0 (Lipopolysaccharides) RN - 0 (Pyridones) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - B72HH48FLU (Infliximab) RN - D7NLD2JX7U (pirfenidone) RN - OP401G7OJC (Etanercept) SB - IM MH - Anti-Inflammatory Agents/*pharmacology MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Antibodies, Monoclonal/*pharmacology MH - Apoptosis/drug effects MH - Cell Survival/drug effects MH - Culture Media MH - Enzyme-Linked Immunosorbent Assay MH - Etanercept MH - Humans MH - Immunoglobulin G/*pharmacology MH - Immunohistochemistry MH - Infliximab MH - Lipopolysaccharides/pharmacology MH - Pyridones/*pharmacology MH - Receptors, Tumor Necrosis Factor MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/biosynthesis EDAT- 2008/04/05 09:00 MHDA- 2008/07/23 09:00 CRDT- 2008/04/05 09:00 PHST- 2007/10/31 00:00 [received] PHST- 2008/01/14 00:00 [revised] PHST- 2008/01/14 00:00 [accepted] PHST- 2008/04/05 09:00 [pubmed] PHST- 2008/07/23 09:00 [medline] PHST- 2008/04/05 09:00 [entrez] AID - S1567-5769(08)00015-5 [pii] AID - 10.1016/j.intimp.2008.01.013 [doi] PST - ppublish SO - Int Immunopharmacol. 2008 May;8(5):679-87. doi: 10.1016/j.intimp.2008.01.013. Epub 2008 Feb 11.