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Over-produced IL-6 decreases blood lipid levels via up-regulation of VLDLR
  1. Misato Hashizume (hashizumemst{at}chugai-pharm.co.jp)
  1. Chugai Pharmaceutical Co.Ltd., Japan
    1. Hiroto Yoshida
    1. Chugai Pharmaceutical Co.Ltd., Japan
      1. Nobuo Koike
      1. Chugai Pharmaceutical Co.Ltd., Japan
        1. Miho Suzuki
        1. Chugai Pharmaceutical Co.Ltd., Japan
          1. Masahiko Mihara (miharamsh{at}chugai-pharm.co.jp)
          1. Chugai Pharmaceutical Co.Ltd., Japan

            Abstract

            Objective: Interleukin-6 (IL-6) blockade raises blood lipid levels in rheumatoid arthritis (RA) patients. In this study, we examined the influence of IL-6 on lipid metabolism.

            Methods: Vascular skeletal muscle cells (VSMC) were cultured in the presence of IL-6, soluble IL-6 receptor (sIL-6R), IL-6 + sIL-6R or TNF-α for 24 h. After culture, the expression of very-low-density lipoprotein receptor (VLDLR), low-density lipoprotein receptor (LDLR) and low-density lipoprotein-related protein-1 (LRP-1) were measured by real-time PCR. Human IL-6 was injected into mice twice a day for 2 weeks and then VLDLR expression in several tissues and the change of total cholesterol (T-Chol) and triglyceride (TG) levels were investigated. Finally, the effect of anti-IL-6 receptor (IL-6R) antibody injection on blood lipid levels was examined.

            Results: IL-6 + sIL-6R significantly induced expression of VLDLR mRNA in VSMC, but IL-6 or sIL-6R alone and TNF-α did not do so. None of these cytokines induced LDLR and LRP-1 mRNA expression. IL-6 injection into mice significantly increased the expression of VLDLR in heart, adipose tissue and liver and decreased T-Chol and TG levels. The injection of anti-IL-6R antibody normalized the reduced levels of T-Chol and TG caused by IL-6 injection, whereas it had no influence on the levels of T-Chol and TG in normal mice.

            Conclusions: Over-produced IL-6 decreased blood lipid levels by increasing VLDLR expression in several tissues. Therefore, we conclude that IL-6 blockade normalizes reduced lipid levels caused by IL-6, but does not affect normal lipid metabolism.

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