Inflammatory response during hyperglycemia and hyperinsulinemia in a porcine endotoxemic model: the contribution of essential organs.
BACKGROUND
During euglycemia acute hyperinsulinemia diminishes the cytokine response to endotoxin [Lipopolysaccharide (LPS)] exposure. In this study we elucidated whether acute hyperglycemia and hyperinsulinemia modify the cytokine content in several organs during LPS challenge in a porcine model.


METHODS
Pigs (35-40 kg) were randomized to either normoglycemia (group 1, n = 8) or hyperglycemia and hyperinsulinemia (group 2, n = 8), anesthetized and mechanically ventilated. Both groups received a 180-min intravenous infusion of LPS (total 10 microg kg(-1)). Groups 1 and 2 were clamped at plasma glucose concentrations of 5 mM and 15 mM, respectively. Group 1 maintained a baseline insulin level while the hyperglycemic group exhibited increased insulin levels.


RESULTS
Circulating cytokines, cytokine mRNA and cytokine protein content were examined in the heart, liver, kidneys, lungs, spleen, adipose and muscle tissue. After LPS exposure, in both groups vast and equal plasma cytokines were elicited by approximately 70-5000-fold. A 10-fold higher level of IL-10, IL-6 and TNF-alpha protein was found in kidney tissue compared to the other organs together with a 3-10-fold increase of TNF-alpha in adipose tissue. However, cytokine mRNAs as well as organ function were without statistical difference between the groups.


CONCLUSIONS
Endotoxemia elicited a pronounced cytokine response in both plasma and at organ level. The kidneys and adipose tissue showed the highest cytokine protein content. Acute hyperglycemia apparently counteracts the well-established anti-inflammatory effects of insulin on the inflammatory response in a LPS challenged porcine model. Whether the observation can be extrapolated to more long-term stress-exposure remains to be clarified.
Brix-Christensen
V
V
Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark. brixchr@dadlnet.dk
Gjedsted
J
J
Andersen
S K
SK
Vestergaard
C
C
Nielsen
J
J
Rix
T
T
Nyboe
R
R
Andersen
N T
NT
Larsson
A
A
Schmitz
O
O
Tønnesen
E
E
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000032:analysis* / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications* / Q000276:immunology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D006943:Hyperglycemia / Q000150:complications*; D006946:Hyperinsulinism / Q000150:complications*; D007249:Inflammation / Q000209:etiology*; D007328:Insulin / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine
D001786:Blood Glucose; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012333:RNA, Messenger; D006854:Hydrocortisone