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. 2010 Dec 13;5(12):e14328.
doi: 10.1371/journal.pone.0014328.

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases

Olaf Schultz  1 , Frank Oberhauser, Jasemine Saech, Andrea Rubbert-Roth, Moritz Hahn, Wilhelm Krone, Matthias Laudes
Affiliations

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases

Olaf Schultz et al. PLoS One. .

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.

Methodology/principal findings: 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/significance: 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.

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Conflict of interest statement

Competing Interests: This study was supported by a grant from Chugai/Roche Pharmaceuticals to Matthias Laudes. This company distributes the drug tocilizumab. Matthias Laudes and Andrea Rubbert-Roth received lecture fees from the same company. The company does not alter the adherence to all the PLoS ONE policies on sharing data and material.

Figures

Figure 1
Figure 1. Effect of IL-6 inhibition on inflammatory parameters in human subjects.
Data are expressed as Means ± SEM. * = p<0.05.
Figure 2
Figure 2. Effect of IL-6 inhibition on body weight and adipokine serum levels in human subjects.
Data are expressed as Means ± SEM. * = p<0.05.
Figure 3
Figure 3. Effect of IL-6 inhibition on insulin sensitivity of human subject.
Data are expressed as Means ± SEM. * = p<0.05.
Figure 4
Figure 4. Effect of IL-6 inhibition on lipoprotein (a) levels in human subjects.
Data are expressed as Means ± SEM of lipoprotein (a) levels x-fold compared to time point 0 month. * = p<0.05.
See this image and copyright information in PMC

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