Copyright 2000 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2000
We read with great interest the article by Sakurai and Hashizume1 that reported a rare case involving the deterioration of rheumatoid arthritis (RA) after the administration of troglitazone, since peroxisome proliferator–activated receptors (PPARs) are a current topic in medicine. We would like to add a few comments in regard to this interesting case report. The authors stated that "the in vivo antiinflammatory [sic] effect of troglitazone is yet to be elucidated." Indeed, synthetic thiazolidinediones, as well as the natural ligand 15-deoxy-Δ12,14-prostaglandin J2, are expected to have anti-inflammatory properties, because PPAR-γ reduces monocyte secretion of interleukin 1β, interleukin 6, and tumor necrosis factor α.2 PPAR-γ activation actually inhibits the activation of nuclear factor κB, activation protein 1, and signal transducer and activator of transcription activities, 3 important factors that regulate cytokine gene expression by binding to their promoters.3 However, the potential weakness of studies that suggest the correlation between PPAR-γ and inflammatory processes is that significant effects in monocytes and macrophages were obtained only when high concentrations (micromolar range) of PPAR-γ agonists were used. This may be the reason why in vivo studies have never been published in the medical literature. Although PPARs have been known to affect many biological functions, eg, adipocyte differentiation, lipid metabolism, anti-inflammatory properties, and tumor cell growth arrest,4 their other medical roles remain to be clarified. Further clinical studies will be required before PPARs ligands can be widely used as therapeutic agents.
Inoue K, Kawahito Y, Sano H. Troglitazone as an Anti-inflammatory Agent. Arch Intern Med. 2000;160(19):3004. doi:
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