@Article{,
AUTHOR = {Anja Ten Brinke, David W. C. Dekkers, Silla M. Notten, Miriam L. Karsten, Els R. de Groot, Lucien A. Aarden},
TITLE = {4-Hydroxy-oxyphenbutazone is a potent inhibitor of cytokine production},
JOURNAL = {European Cytokine Network},
VOLUME = {16},
YEAR = {2005},
NUMBER = {2},
PAGES = {144--151},
URL = {http://www.techscience.com/ECN/v16n2/66227},
ISSN = {1952-4005},
ABSTRACT = {4-hydroxy-oxyphenbutazone (4OH-OPB), is currently in phase II trials for its immunosuppressive
effect in patients with rheumatoid arthritis. 4OH-OPB and other compounds related to phenylbutazone were
tested for their effect on in vitro cytokine production by monocytes and lymphocytes present in peripheral
mononuclear cells (PBMC) or whole blood (WB) cultures, and compared against phenylbutazone and oxyphenbutazone,
two known anti-inflammatory drugs. In PBMC cultures, 4OH-OPB was by far the most potent
inhibitor, and both monokines and Th1 and Th2 lymphokines were efficiently inhibited at low concentrations. In
WB cultures, 4OH-OPB was less effective than in PBMC cultures, but was still the best inhibitor of lymphokine
production and, furthermore, was the only inhibitor of monokine production. The increase in 4OH-OPB
concentration needed to induce the same inhibition of cytokine production in WB as in PBMC culture could be
mimicked by the addition of erythrocytes to the PBMC cultures. Experiments with radioactively-labeled
4OH-OPB suggest that 4OH-OPB is taken up very rapidly into erythrocytes and is secreted by the erythrocytes
with much slower kinetics via a multidrug-resistance-associated protein. The secreted compound is most likely
structurally different from 4OH-OPB, as in PBMC and WB cultures, the inhibition of cytokine production seems
to be caused by a different mechanism. In PBMC cultures, the inhibition of cytokine production is accompanied
by a loss of cell viability, while this is not the case when 4OH-OPB inhibits cytokine production in WB. Our data
suggest that 4OH-OPB may be useful as an immunosuppressive drug for patients with inflammatory diseases.},
DOI = {}
}