Effects of Inhibition of Interleukin-6 Signalling on Insulin Sensitivity and Lipoprotein (A) Levels in Human Subjects with Rheumatoid Diseases

• Published in: PloS one Vol. 5; no. 12; p. e14328
• Main Authors: Schultz, Olaf, Oberhauser, Frank, Saech, Jasemine, Rubbert-Roth, Andrea, Hahn, Moritz, Krone, Wilhelm, Laudes, Matthias
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.12.2010; Public Library of Science (PLoS)
• Subjects: Adipokines - blood; Adiponectin; Adult; Aged; Analysis; Antibodies; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Apolipoproteins; Arthritis, Rheumatoid - metabolism; Blood cholesterol; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Clinical trials; Cytokines; Cytokines - metabolism; Diabetes; Diabetes and Endocrinology; Diabetes mellitus; Diabetes Mellitus, Type 2 - metabolism; Diabetes therapy; Diabetics; Drug therapy; Female; Health risks; High density lipoprotein; Human subjects; Humans; Immunoglobulins; Immunology; Inflammation; Inhibition; Insulin; Insulin - metabolism; Insulin Resistance; Interleukin; Interleukin 6; Interleukin 6 receptors; Interleukin-6 - metabolism; Interleukins; Internal medicine; Kidney diseases; Leptin; Lipoprotein A; Lipoprotein(a) - metabolism; Lipoproteins; Low density lipoprotein; Low density lipoproteins; Male; Medical research; Medicine; Metabolism; Middle Aged; Nutrition/Obesity; Parameter sensitivity; Pathogenesis; Rheumatoid arthritis; Rodents; Sensitivity; Serum levels; Signal Transduction; Signaling; Studies; Triglycerides; Tumor necrosis factor-TNF; Type 2 diabetes; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014328

Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab. 11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a) (Lp (a)) were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a) levels significantly decreased. Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a) serum levels, which might reduce the cardiovascular risk of human subjects.