Type 2 diabetes mellitus is associated with impaired cytokine response and adhesion molecule expression in human endotoxemia.
OBJECTIVE
Type 2 diabetes is associated with an increased risk of acquiring infectious diseases and developing sepsis. This may partly be due to immune dysfunction. We investigated the in vivo innate immune response of type 2 diabetic persons to an intravenous injection of E. coli lipopolysaccharide (LPS).


METHODS
After ethics approval, informed consent and a thorough physical examination, 19 type 2 diabetic patients and 23 healthy controls were included. LPS was given as an intravenous bolus injection of 0.3 ng/kg. Physiological variables, white blood cell count, and plasma concentrations of tumour necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and the adhesion molecules E-selectin, vascular adhesion molecule (VCAM)-1, and intracellular adhesion molecule (ICAM)-1 were measured hourly for 8 h.


RESULTS
LPS injection induced a systemic inflammatory response with increases in neutrophils, temperature, heart rate and plasma concentrations of cytokines and adhesion molecules in healthy and type 2 diabetic volunteers. Type 2 diabetes was associated with less pronounced LPS-induced increases in TNF, IL-1ra, VCAM-1 and ICAM-1. There was a trend towards an attenuated upregulation of E-selectin in diabetics, even though the plasma concentration tended to be generally higher compared to healthy controls.


CONCLUSIONS
Patients with type 2 diabetes exhibit an attenuated increase in plasma levels of TNF and IL-1ra, as well as an attenuated upregulation of VCAM-1 and ICAM-1 to LPS in vivo. This finding may provide a mechanistic explanation for the adverse outcome seen during infectious diseases in diabetic patients.
Andreasen
Anne Sofie
AS
Centre of Inflammation and Metabolism, Department of Infectious Diseases, University Hospital Rigshospitalet, Rigshospitalet-M 7641, Blegdamsvej 9, 2100, Copenhagen, Denmark. sofie_andreasen@msn.com
Pedersen-Skovsgaard
Theis
T
Berg
Ronan M G
RM
Svendsen
Kira Dynnes
KD
Feldt-Rasmussen
Bo
B
Pedersen
Bente K
BK
Møller
Kirsten
K
D056704:Adaptive Immunity / Q000276:immunology; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D019446:Endotoxemia / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C044101:endotoxin, Escherichia coli