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.