Glutamine Supplementation Preserves Skeletal Muscle Force During Acute Inflammation

Abstract

Acute and chronic inflammatory diseases are often associated with respiratory and skeletal muscle weakness and potential muscle wasting. Decrements in muscle function under these conditions may be mediated in part by elevated levels of catabolic cytokines such as TNFa, which has been shown to independently and acutely reduce contractile function. Glutamine has been shown to protect in various tissues against inflammatory insults, in part by the up-regulation of protective heat shock proteins (HSP) and/or reducing catabolic cytokine levels. PURPOSE: To test the hypothesis that acute Glutamine (GLN) supplementation can counteract skeletal muscle contractile dysfunction occurring in response to an inflammatory insult by elevating muscle Hsp expression and reducing systemic and muscle cytokines. METHODS: Mice received 5mg/kg Lipopolysaccharide (LPS) concurrently with 1g/kg GLN or saline (Sal) vehicle treatments. Plantarflexor isometric force-production was measured 2 hours post-injection in anesthetized mice with a lever/footplate system able to simultaneously control length and measure force. Sciatic nerve stimulation was used to elicit 10 repetitions (5-sec rest) to capture maximal force and fatigue. Immediately after the last contraction, blood and gastrocnemius muscles were collected. Serum and muscle TNFa and IL-6 were quantified by Elisa and muscle Hsp72 and Hsp25 by Western blot. RESULTS: Sal/LPS-treatment was associated with a 33% reduction in maximal force and elevated serum TNFa and IL-6 compared to the Sal/Sal group (p<.05). GLN completely prevented the force decrement with LPS, however, GLN alone did not affect force (i.e., no differences among Sal/Sal, GLN/Sal, and GLN/LPS groups). No group differences were found for muscle fatigue. Additionally, no main effect for GLN was found on muscle or serum TNFa or IL-6, however muscle Hsp72 was significantly reduced by 47% in the GLN/LPS group compared to the other 3 groups. CONCLUSIONS: GLN supplementation provides an effective, novel, and clinically applicable means of preserving muscle force under conditions of acute inflammation. These data indicate that preservation of force is not dependent on reductions in muscle or serum cytokines or elevated Hsp levels, as these measures were not altered with GLN treatment. Supported by funding from NSMRC