Table 5.
Inflammatory mediators associated with critical illness and effects in muscle
| Inflammatory Mediator | Molecular Mass, kDa | Effects in Skeletal Muscle |
|---|---|---|
| TNF-α (cachectin) | 26 (mature secreted form: 17) | Also expressed in type II muscle fibers (550) |
| Depolarization of plasma membrane (712) | ||
| Na+-current inhibition, left shift of Na+ channel activation and inactivation (274) | ||
| Activation of PKC-mediated Na+ channel phosphorylation (148) | ||
| Induces muscle proteolysis and atrophy (148) | ||
| Alters resting Ca2+ levels (decrease in myotubes) (741) | ||
| No change in tetanic Ca2+ amplitudes in muscle fibers (741) | ||
| Decreases Ca2+ transient amplitudes by 50% (in myotubes) (741) | ||
| Depresses tetanic force production in limb and diaphragm muscle (571) | ||
| Activates ubiquitin-proteasome pathway (227,428) | ||
| Increase major histocompatibility complex II surface expression (in combination with IFN-γ) in human muscle cells (359) | ||
| Activation of NF-κB (573) | ||
| Downregulation of MyoD inhibits myogenic differentiation (280) | ||
| Induces insulin resistance in muscle (248) | ||
| IL-1 | 13–17 (precursors: 33) | Produced by activated macrophages; also expressed in muscle fibers in health (619), following exercise (101), and in inflammatory myopathies (26) |
| IL-1α: primarily membrane-bound | Associates with RyR1, blocks SR Ca2+-release, and decreases SR Ca2+ leak in muscle fibers (220) | |
| IL-1β: secreted form | Upregulates iNOS expression (4) | |
| Induces skeletal muscle proteolysis [IL-1α (785), but maybe not IL-1β (228)] | ||
| Stimulates IL-6 production in skeletal muscle cells (IL-1β) (445) | ||
| Stimulates prostaglandin E2 (PGE2) production and proteolysis (250) | ||
| Ubiquitin gene expression ↑ (437) or ⇆ (228) | ||
| Inhibition of protein synthesis (132) | ||
| IL-6 | 23–30 (glycosylation diversity) | Produced by activated macrophages and T-cells, tumor cells, but also produced by muscle fibers (type I > type II) (550) |
| No effect on ubiquitin expression (437) | ||
| Promotes infiltration of myocytes with prostaglandins (780) | ||
| Both pro- and anti-inflammatory actions in critical illness (24) | ||
| Induces skeletal muscle protein breakdown (in rats) (259) | ||
| Reduces insulin-stimulated glucose uptake in muscle (364) | ||
| IL-10 | 18 (unglycosylated in humans) | Anti-inflammatory cytokine (780) |
| Prevents skeletal muscle from IL-6-induced defects in insulin action (364) | ||
| IFN-γ | 20–25 | Produced by activated T-cells and natural killer cells but also in muscle fibers following muscle injury (118) |
| Required for muscle regeneration (118) | ||
| Inhibits protein translation in muscle by stimulating NO synthase activity (223) | ||
| Modulator of TNF-α signaling in muscle (myotubes: downregulation of TNF-R2 and increased NF-κB activity) (710) | ||
| Ubiquitin gene expression ↑ (437) |