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Alteration of somatotropic function by proinflammatory cytokines
1Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey 17033, USA. rfrost@psu.edu <rfrost@psu.edu>
Journal of Animal Science
|October 9, 2004
Summary
Infections disrupt muscle growth by altering protein synthesis and leading to growth hormone resistance. Understanding these mechanisms is key to developing therapies for muscle wasting during illness.
Area of Science:
- Biochemistry
- Physiology
- Immunology
Background:
- Infections divert amino acids from muscle growth to acute-phase protein synthesis in the liver.
- Skeletal muscle protein loss during infection impairs function and increases mortality.
- Proinflammatory cytokines and altered Insulin-like Growth Factor (IGF) system contribute to muscle wasting.
Purpose of the Study:
- To investigate the mechanisms by which infections cause skeletal muscle wasting.
- To determine if proinflammatory cytokines directly affect muscle protein synthesis or indirectly via the IGF system.
- To understand the development of growth hormone (GH) resistance during infection.
Main Methods:
- Analysis of plasma concentrations of IGF-I, somatotropin, and IGF-binding proteins (IGFBPs) in infected animals.
- Investigation of IGFBP-3 proteolysis and IGFBP-1 accumulation in skeletal muscle.
- Examination of the role of proinflammatory cytokines and lipopolysaccharide (LPS) in regulating IGF-I and IGFBP-1 gene transcription in muscle cells.
Main Results:
- Plasma IGF-I concentrations decrease significantly during infection, indicating GH resistance.
- IGFBP-1 levels increase, potentially inhibiting IGF-dependent protein synthesis in muscle.
- Proinflammatory cytokines, induced by LPS, are upregulated in skeletal muscle, suggesting local regulation of IGF-I synthesis.
Conclusions:
- Infections induce GH resistance and muscle wasting through complex interactions involving the IGF system and local cytokine production.
- Local cytokine expression in skeletal muscle may inhibit autocrine IGF-I synthesis.
- Further research is needed to elucidate the precise mechanisms of GH resistance and develop therapeutic strategies to preserve muscle mass during infection.