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 in flammation syndrome or sepsis. Elevated plasma lactate concentrations may b e caused by cytokine-mediated alterations in specific organ systems respons ible for lactate homeostasis. The role of interleukin 1 (IL-1) in inducing hyperlactatemia and derangements in skeletal muscle and hepatic lactate met abolism was investigated by examining the consequences of infusing IL-1 con tinuously into normal rats. Methods: Male Sprague-Dawley rats were anesthet ized, and catheters were placed in the jugular vein. Rats were allowed to r ecover for 48 hours and were infused subsequently with either saline (contr ol) or human recombinant IL-1 alpha (20 mu g/kg/d) for 6 days. On day 6, pl asma, liver, and muscle samples were extracted and assayed for lactate and pyruvate dehydrogenase (PDH) activity. Results: Plasma glucose concentratio ns were not different in the two groups. IL-1 infusion resulted in a twofol d (p < .05) increase in the plasma lactate concentration compared with cont rols. IL-1 infusion also resulted in an elevated lactate content in skeleta l muscle (p < .05) but not in liver. The proportion of PDH in the active fo rm (PDHa) was reduced significantly (p < .05) in the skeletal muscle of ani mals infused with IL-1 compared with controls. In contrast to muscle, hepat ic PDHa did not differ between the two groups. Total PDH complex activity w as not affected in either liver or skeletal muscle. Conclusions: IL-1 infus ion results in hyperlactatemia, increased skeletal muscle lactate, and a re duced PDHa in skeletal muscle. We conclude that IL-1 is a potential mediato r of the derangements in lactate metabolism in skeletal muscle but not in l iver.