**2.1.1 Anti-inflammatory actions**

The anti-inflammatory actions of fenofibrate were reported in Nature in 1998 (Staels et al., 1998). PPAR-α ligand: fenofibrate inhibited cyclooxygenase-2 (COX-2) expression and prostaglandin production by suppressing the transcription of COX-2 genes through the inhibition of nuclear factor κB (NF-κB: transcription factor) signals. Fenofibrate administration decreased the inflammatory parameters including serum levels of IL-6, fibrinogen, and C-reactive protein (CRP) in coronary disease patients and the patients with hypertriglyceridemia (Tsimihodimos et al., 2004; Muhlestein et al., 2006).

Closed circles represent fenofibrate; open circles represent statins. mean ± S.D. Wilcoxon signed rank test versus baseline, \*\* P <0.01, Mann-Whitney U test versus group

Fig. 1. Changes in prednisolone (PSL) dosage.

reviewed in this section. These activities may be tightly associated with anti-aging actions of fenofibrate. Three large-scale, randomized, comparative clinical studies of fenofibrate ("DAIS", "FIELD" and "ACCORD"), in which intervention was performed in patients with

Previous studies reported the involvement of various clinical parameters in anti-aging actions of fenofibrate (Schlesinger et al., 2009). In particular, chronic, systemic, silent, lowgrade inflammation, named inflammaging is the target for intensive research in aging study (Goto, 2008b). Ross et al. defined arteriosclerosis as "chronic vascular inflammation" resulting from an interaction between oxidized lipid and macrophages (Ross, 1999). Inflammation is involved in the onset of arteriosclerotic disorders and acute coronary syndrome. Furthermore, oxidative stress that can induce a vicious cycle of chronic inflammation has been believed to be the major driving force to promote aging (Yu &

Uric acid has recently been considered to be a prognostic factor for the onset of DM and dementia that may accelerate aging (Hikita et al., 2007; Abate et al., 2004; Martinon et al., 2006), although an excess level of uric acid is the primary incite for gouty attack (Schlesinger

The anti-inflammatory actions of fenofibrate were reported in Nature in 1998 (Staels et al., 1998). PPAR-α ligand: fenofibrate inhibited cyclooxygenase-2 (COX-2) expression and prostaglandin production by suppressing the transcription of COX-2 genes through the inhibition of nuclear factor κB (NF-κB: transcription factor) signals. Fenofibrate administration decreased the inflammatory parameters including serum levels of IL-6, fibrinogen, and C-reactive protein (CRP) in coronary disease patients and the patients with

**5.3**

●Fenofibrate ○Statin

**p<0.05**

mean±S.D. \*\*:p<0.01

**2.0**

\*\*

hypertriglyceridemia (Tsimihodimos et al., 2004; Muhlestein et al., 2006).

**3.6**

Wilcoxon signed rank test versus baseline, \*\* P <0.01, Mann-Whitney U test versus group

Closed circles represent fenofibrate; open circles represent statins. mean ± S.D.

投与前 **6**ヵ月後

Baseline after 6 months

**0**

Fig. 1. Changes in prednisolone (PSL) dosage.

**2**

**4**

**6**

**8**

**10**

(mg/day)

**4.5**

type II diabetes mellitus (DM), were published since 2000.

**2.1 Anti-aging activities** 

Chung, 2001; Romano et al., 2010).

**2.1.1 Anti-inflammatory actions** 

et al., 2009).

We compared the anti-inflammatory effects of fenofibrate and statins in 44 patients with a chronic inflammatory disorder: rheumatoid arthritis (RA) (Goto, 2010). Japanese patients with RA and dyslipidemia were randomly divided into 2 groups: fenofibrate (Lipidil, Kaken Pharmaceutical Co., Ltd., micronized fenofibrate at 200 mg/day, n=23) and statins (n=21) groups. After 6-month administration, the laboratory data were compared, and pain was evaluated using the visual analogue scale (VAS) and dose change of prednisolone (PSL) was monitored. The VAS scores significantly decreased in the fenofibrate (from 49.1 to 14.7 mm, p<0.0001) and statin (from 47.4 to 20.2 mm, p<0.001) groups. The dose of PSL significantly reduced only in the fenofibrate group (from 3.58 to 2.00 mg/day, p<0.01). The reduction rate was also significantly better than in the statin group (Fig. 1).

In the fenofibrate group, a significant correlation was between the rate of change in the ΔVAS score and that in the ΔCRP level (Fig.2. p<0.05). The results suggest that, in patients with RA, fenofibrate exhibits more potent anti-inflammatory effects compared to statins.

Spearman rank correlation coefficient

VAS visual analogue scale; HDL-C high-density lipoprotein-cholesterol; RF rheumatoid factor; CRP Creactive protein; ESR erythrocyte sedimentation rate; PSL prednisolone

Fig. 2. Fenofibrate administration group: correlation between anti-inflammatory markers and ΔVAS.
