Evidence that acute hyperinsulinaemia increases the cytokine content in essential organs after an endotoxin challenge in a porcine model.
BACKGROUND
Insulin has anti-inflammatory effects, as evaluated by its ability to reduce the plasma concentrations of cytokines. However, the inflammatory processing at the organ level is far less well established. The cytokine content in several organs after endotoxin (lipopolysaccharide, LPS) exposure and the effect of hyperinsulinaemia was examined.


METHODS
Pigs (35-40 kg) were randomized into four groups, anaesthetized and mechanically ventilated for 570 min: group 1 (anaesthesia only; n = 10), group 2 (hyperinsulinaemic euglycaemic clamp, HEC; n = 9), group 3 (LPS; n = 10) and group 4 (LPS + HEC; n = 9). LPS was infused intravenously for 180 min (total dosage, 10 microg/kg). At the end of the study, i.e. 330 min after the termination of LPS or equivalent, cytokine mRNA and cytokine protein contents in the lungs, heart, liver, adipose tissue and spleen were measured.


RESULTS
Hyperinsulinaemia led to increased interleukin-10 (IL-10) protein content in the heart and liver (by 40% and 28%, respectively) in comparison with normoinsulinaemic animals (P < 0.01 and P = 0.02, respectively), and increased tumour necrosis factor-alpha (TNF-alpha) protein content in the heart (P = 0.02). Animals exposed to LPS exhibited reduced TNF-alpha, IL-6 and IL-8 protein content in the heart (P = 0.02, P < 0.001 and P = 0.01, respectively). In the kidneys and adipose tissue, a particularly large cytokine protein content was observed.


CONCLUSIONS
The findings strongly substantiate the role of insulin as an immune-modifying hormone at organ level during baseline and after an endotoxin challenge. Moreover, the kidneys and adipose tissue appear to be pivotal organs in terms of cytokine content shortly after endotoxin exposure, but the complexity remains to be clarified.
Brix-Christensen
V
V
Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus C, Denmark. brixchr@dadlnet.dk
Vestergaard
C
C
Andersen
S K
SK
Krog
J
J
Andersen
N T
NT
Larsson
A
A
Schmitz
O
O
Tønnesen
E
E
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014018:Tissue Distribution
D001786:Blood Glucose; D016207:Cytokines; D004731:Endotoxins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008070:Lipopolysaccharides; D012333:RNA, Messenger