Overproduced interleukin 6 decreases blood lipid levels via upregulation of very-low-density lipoprotein receptor.
BACKGROUND
Interleukin 6 (IL6) blockade raises blood lipid levels in patients with rheumatoid arthritis.


OBJECTIVE
To examine the influence of IL6 on lipid metabolism.


METHODS
Vascular smooth muscle cells (VSMC) were cultured in the presence of IL6, soluble IL6 receptor (sIL6R), IL6+sIL6R or tumour necrosis factor alpha (TNFalpha) 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 IL6 was injected into mice twice a day for 2 weeks and then VLDLR expression in several tissues and the change of total cholesterol (TC) and triglyceride (TG) levels were investigated. Finally, the effect of anti-IL6 receptor (IL6R) antibody injection on blood lipid levels was examined.


RESULTS
IL6+sIL6R significantly induced expression of VLDLR mRNA in VSMC (8.6-fold, p<0.05), but IL6 or sIL6R alone and TNFalpha did not do so. None of these cytokines induced LDLR and LRP-1 mRNA expression. IL6 injection into mice increased the expression of VLDLR in heart, adipose tissue and liver and decreased TC and TG levels. The injection of anti-IL6R antibody normalised the reduced levels of TC and TG caused by IL6 injection, whereas it had no influence on the levels of TC and TG in normal mice.


CONCLUSIONS
Overproduced IL6 decreased blood lipid levels by increasing VLDLR expression in several tissues. It is concluded that IL6 blockade normalises reduced lipid levels caused by IL6, but does not affect normal lipid metabolism.
Hashizume
Misato
M
Product Research Department, Chugai Pharmaceutical Co. Ltd., 1-135 Komakado, Gotemba, Shizuoka, Japan.
Yoshida
Hiroto
H
Koike
Nobuo
N
Suzuki
Miho
M
Mihara
Masahiko
M
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000502:physiology; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects*
D015850:Interleukin-6; D008055:Lipids; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011973:Receptors, LDL; D011994:Recombinant Proteins; D014280:Triglycerides; C036053:VLDL receptor; D002784:Cholesterol