Differential lipogenic effects of cilostazol and pentoxifylline in patients with intermittent claudication: potential role for interleukin-6

Cilostazol, a novel oral phosphodiesterase inhibitor, has shown consistent improvement in exercise tolerance in patients with intermittent claudicatio n. (IC). In addition to this effect, cilostazol has previously been shown. to have beneficial effects on the dyslipidemia, i.e., combination of high t riglycerides with low high-density-lipoprotein cholesterol (HDL-Q levels. I nterluekin-6 (IL-6) suppresses the activity of lipoprotein lipase, which mo dulates the metabolism of triglycerides and HDL-C. To determine whether a r eduction of IL-6 contributes to the improvement of lipid profiles, we prosp ectively investigated the effect of cilostazol (n = 16, 100 mg, twice daily ) on the changes of lipid profiles and on the association with the changes of IL-6 compared with those of pentoxifylline (n = 16, 400 mg, bid) in pati ents with IC. After eight weeks of administration of cilostazol to patients with IC, walking distances were increased, associated with a 29% decrease in plasma triglycerides and a 13% increase in HDL-C. No significant changes of lipid profiles in the pentoxifylline and placebo groups were observed a lthough a similar improvement in walking distances was achieved in the pent oxifylline group. IL-6 levels were significantly reduced in patients receiv ing cilostazol as compared with those receiving placebo or pentoxifylline. The cilostazol-induced changes in the IL-6 were positively related to those of triglycerides in the cilostazol group (r = 0.63, P < 0.05) and negative ly related to those of HDL-C (r = - 0.55, P < 0.05). These findings suggest that in addition to consistent improvement of exercise tolerance, cilostaz ol may improve lipid profiles by reducing IL-6 release. However, pentoxifyl line did not affect lipid profiles although a similar improvement of maxima l walking distance (MWD) was achieved. (C) 2001 Elsevier Science Ireland Lt d. All rights reserved.