title: Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine II and Centre of Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Schultz
authors.forename: Frank
authors.initials: F
authors.lastname: Oberhauser
authors.forename: Jasemine
authors.initials: J
authors.lastname: Saech
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert-Roth
authors.forename: Moritz
authors.initials: M
authors.lastname: Hahn
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Krone
authors.forename: Matthias
authors.initials: M
authors.lastname: Laudes
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism*; D017270:Lipoprotein(a) / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D017270:Lipoprotein(a); C502936:tocilizumab