Type 2 diabetes and lipoprotein metabolism affect LPS-induced cytokine and chemokine release in primary human monocytes

Exp Clin Endocrinol Diabetes. 2011 Jun;119(6):370-6. doi: 10.1055/s-0030-1268413. Epub 2010 Nov 22.

Abstract

Aims/hypothesis: Obesity and insulin resistance are characterized by a chronic and low grade state of inflammation and the pro-inflammatory response of monocytes is affected in type 2 diabetes mellitus (T2D). We aimed to investigate whether LPS-induced monocytic cytokine and chemokine release depends on serum lipoprotein parameters in T2D patients.

Methods: Primary human monocytes were isolated from 29 patients with known T2D and from 20 healthy volunteers. Anthropometric and disease-related parameters such as age, gender, BMI, WHR, diabetes duration, diabetes complications, and diabetes control (HbA1c) were documented. Monocytes were stimulated for 18 h with LPS (1 μg/ml). Unstimulated monocytes served as control. The supernatant concentrations of CCL2, CCL3, CCL4, CCL5, MIF and resistin were measured by ELISA.

Results: LPS-stimulation significantly (p<0.001) increased CCL chemokine and resistin concentrations in healthy controls and in patients with T2D, whereas MIF release was not affected in both groups. LPS-induced CCL2 and resistin concentrations were significantly higher in T2D patients when compared to healthy controls. In T2D patients, LPS-induced CCL3 concentration was higher in males when compared to females (p=0.039) and supernatant resistin concentration upon stimulation with LPS showed a significant and positive correlation with age (r=0.6; p=0.001). LPS-induced CCL2 concentration was significantly and positively correlated with serum triglyceride concentration (r=0.4; p=0.009) in T2D patients. Furthermore, LPS-induced CCL4 concentration was significantly and positively correlated with total (r=0.4; p=0.035) and LDL cholesterol (r=0.4; p=0.033) concentration.

Conclusions: LPS responsiveness of monocytes is altered in T2D and is affected by the respective serum lipoprotein metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Culture Techniques
  • Cells, Cultured
  • Chemokines / metabolism*
  • Cohort Studies
  • Cytokines / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Lipoproteins / metabolism*
  • Lipoproteins / physiology
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Monocytes / pathology

Substances

  • Chemokines
  • Cytokines
  • Lipopolysaccharides
  • Lipoproteins