Chronic infusion of interleukin 1 induces hyperlactatemia and altered regulation of lactate metabolism in skeletal muscle.
BACKGROUND
Hyperlactatemia is observed commonly in patients with severe inflammation syndrome or sepsis. Elevated plasma lactate concentrations may be caused by cytokine-mediated alterations in specific organ systems responsible for lactate homeostasis. The role of interleukin 1 (IL-1) in inducing hyperlactatemia and derangements in skeletal muscle and hepatic lactate metabolism was investigated by examining the consequences of infusing IL-1 continuously into normal rats.


METHODS
Male Sprague-Dawley rats were anesthetized, and catheters were placed in the jugular vein. Rats were allowed to recover for 48 hours and were infused subsequently with either saline (control) or human recombinant IL-1alpha (20 microg/kg/d) for 6 days. On day 6, plasma, liver, and muscle samples were extracted and assayed for lactate and pyruvate dehydrogenase (PDH) activity.


RESULTS
Plasma glucose concentrations were not different in the two groups. IL-1 infusion resulted in a twofold (p < .05) increase in the plasma lactate concentration compared with controls. IL-1 infusion also resulted in an elevated lactate content in skeletal muscle (p < .05) but not in liver. The proportion of PDH in the active form (PDHa) was reduced significantly (p < .05) in the skeletal muscle of animals infused with IL-1 compared with controls. In contrast to muscle, hepatic PDHa did not differ between the two groups. Total PDH complex activity was not affected in either liver or skeletal muscle.


CONCLUSIONS
IL-1 infusion results in hyperlactatemia, increased skeletal muscle lactate, and a reduced PDHa in skeletal muscle. We conclude that IL-1 is a potential mediator of the derangements in lactate metabolism in skeletal muscle but not in liver.
Vary
T C
TC
Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey 17033, USA.
O'Neill
P
P
Cooney
R N
RN
Maish
G
G
Shumate
M
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006706:Homeostasis; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D001786:Blood Glucose; D007375:Interleukin-1; D011768:Pyruvate Dehydrogenase Complex; D011994:Recombinant Proteins; D019344:Lactic Acid