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Inhibition Of Transcription Factors By Anti‐Inflammatory And Anti‐Rheumatic Drugs: Can Variability In Response Be Overcome?
Author(s) -
Handel Malcolm L,
Nguyen Ly Qq,
Lehmann Thomas P
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03216.x
Subject(s) - rheumatoid arthritis , medicine , pharmacology , transcription factor , adverse effect , activator (genetics) , drug , tumor necrosis factor alpha , inflammatory response , bioinformatics , inflammation , immunology , receptor , biology , gene , biochemistry
SUMMARY 1. The drugs used in the treatment of rheumatoid arthritis (RA) form a diverse group with unpredictable adverse effects, mostly weak efficacy and variable responses. Despite their differences, a common feature of many anti‐inflammatory and disease‐modifying anti‐rheumatic drugs (DMARD) is inhibition of pro‐inflammatory transcription factors, particularly nuclear factor (NF)‐κB and activator protein (AP)‐1. 2. The present brief review identifies those drugs capable of inhibiting transcription factors, particularly steroids, gold salts, D ‐penicillamine, cyclosporine A and possibly salicylates. 3. The newer biological inhibitors of tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β are capable of indirect inhibition of NF‐κB activation, although even with these potent agents the problem of variability in response has not disappeared. 4. The development of selective inhibitors of the transcription factor NF‐κB should have the benefit of the anti‐inflammatory drugs and DMARD, both new and old. 5. It is hypothesized that this strategy will overcome much of the variability in the therapeutic response and adverse effects that limit the usefulness of the exisiting drugs in the treatment of RA.