Abstract
Muscle dysfunction is common in patients with adult respiratory distress syndrome and is associated with morbidity that can persist for years after discharge. In a mouse model of severe influenza A pneumonia, we found the proinflammatory cytokine IL-6 was necessary for the development of muscle dysfunction. Treatment with a Food and Drug Administration–approved Ab antagonist to the IL-6R (tocilizumab) attenuated the severity of influenza A–induced muscle dysfunction. In cultured myotubes, IL-6 promoted muscle degradation via JAK/STAT, FOXO3a, and atrogin-1 upregulation. Consistent with these findings, atrogin-1 +/2 and atrogin-1 2 / 2 mice had attenuated muscle dysfunction following influenza infection. Our data suggest that inflammatory endocrine signals originating from the injured lung activate signaling pathways in the muscle that induce dysfunction. Inhibiting these pathways may limit morbidity in patients with influenza A pneumonia and adult respiratory distress syndrome.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 484-493 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 202 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 15 2019 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
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Influenza A virus infection induces muscle wasting via IL-6 regulation of the E3 ubiquitin ligase atrogin-1. / Radigan, Kathryn A.; Nicholson, Trevor T.; Welch, Lynn C.; Chi, Monica; Amarelle, Luciano; Angulo, Martín; Shigemura, Masahiko; Shigemura, Atsuko; Runyan, Constance E.; Morales-Nebreda, Luisa; Perlman, Harris R; Ceco, Ermelinda; Lecuona, Emilia; Dada, Laura; Misharin, Alexander; Mutlu, Gokhan M.; Sznajder, Jacob I; Budinger, GR Scott.
In: Journal of Immunology, Vol. 202, No. 2, 15.01.2019, p. 484-493.Research output: Contribution to journal › Article
TY - JOUR
T1 - Influenza A virus infection induces muscle wasting via IL-6 regulation of the E3 ubiquitin ligase atrogin-1
AU - Radigan, Kathryn A.
AU - Nicholson, Trevor T.
AU - Welch, Lynn C.
AU - Chi, Monica
AU - Amarelle, Luciano
AU - Angulo, Martín
AU - Shigemura, Masahiko
AU - Shigemura, Atsuko
AU - Runyan, Constance E.
AU - Morales-Nebreda, Luisa
AU - Perlman, Harris R
AU - Ceco, Ermelinda
AU - Lecuona, Emilia
AU - Dada, Laura
AU - Misharin, Alexander
AU - Mutlu, Gokhan M.
AU - Sznajder, Jacob I
AU - Budinger, GR Scott
PY - 2019/1/15
Y1 - 2019/1/15
N2 - Muscle dysfunction is common in patients with adult respiratory distress syndrome and is associated with morbidity that can persist for years after discharge. In a mouse model of severe influenza A pneumonia, we found the proinflammatory cytokine IL-6 was necessary for the development of muscle dysfunction. Treatment with a Food and Drug Administration–approved Ab antagonist to the IL-6R (tocilizumab) attenuated the severity of influenza A–induced muscle dysfunction. In cultured myotubes, IL-6 promoted muscle degradation via JAK/STAT, FOXO3a, and atrogin-1 upregulation. Consistent with these findings, atrogin-1 +/2 and atrogin-1 2 / 2 mice had attenuated muscle dysfunction following influenza infection. Our data suggest that inflammatory endocrine signals originating from the injured lung activate signaling pathways in the muscle that induce dysfunction. Inhibiting these pathways may limit morbidity in patients with influenza A pneumonia and adult respiratory distress syndrome.
AB - Muscle dysfunction is common in patients with adult respiratory distress syndrome and is associated with morbidity that can persist for years after discharge. In a mouse model of severe influenza A pneumonia, we found the proinflammatory cytokine IL-6 was necessary for the development of muscle dysfunction. Treatment with a Food and Drug Administration–approved Ab antagonist to the IL-6R (tocilizumab) attenuated the severity of influenza A–induced muscle dysfunction. In cultured myotubes, IL-6 promoted muscle degradation via JAK/STAT, FOXO3a, and atrogin-1 upregulation. Consistent with these findings, atrogin-1 +/2 and atrogin-1 2 / 2 mice had attenuated muscle dysfunction following influenza infection. Our data suggest that inflammatory endocrine signals originating from the injured lung activate signaling pathways in the muscle that induce dysfunction. Inhibiting these pathways may limit morbidity in patients with influenza A pneumonia and adult respiratory distress syndrome.
UR - http://www.scopus.com/inward/record.url?scp=85059928675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059928675&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1701433
DO - 10.4049/jimmunol.1701433
M3 - Article
VL - 202
SP - 484
EP - 493
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -