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
| Autor: | J.M. Nakashima, L. Feng, S.N. Giri, S.B. Margolin, K.J. Grattendick |
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| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
Drug Cell Survival Pyridones medicine.drug_class media_common.quotation_subject medicine.medical_treatment Immunology Anti-Inflammatory Agents Apoptosis Enzyme-Linked Immunosorbent Assay Pharmacology Monoclonal antibody Receptors Tumor Necrosis Factor Etanercept Humans Immunology and Allergy Medicine media_common Tumor Necrosis Factor-alpha business.industry Anti-Inflammatory Agents Non-Steroidal Antibodies Monoclonal Pirfenidone Immunohistochemistry Infliximab In vitro Culture Media Cytokine Immunoglobulin G Tumor necrosis factor alpha business medicine.drug |
| Zdroj: | International Immunopharmacology. 8:679-687 |
| ISSN: | 1567-5769 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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