tetano
Editor, Senior Moderator
J Immunol. 2018 Dec 7. pii: ji1701433. doi: 10.4049/jimmunol.1701433. [Epub ahead of print]
[h=1]Influenza A Virus Infection Induces Muscle Wasting via IL-6 Regulation of the E3 Ubiquitin Ligase Atrogin-1.[/h] Radigan KA[SUP]1[/SUP], Nicholson TT[SUP]1[/SUP], Welch LC[SUP]1[/SUP], Chi M[SUP]1[/SUP], Amarelle L[SUP]1,[/SUP][SUP]2[/SUP], Angulo M[SUP]1,[/SUP][SUP]2[/SUP], Shigemura M[SUP]1[/SUP], Shigemura A[SUP]1[/SUP], Runyan CE[SUP]1[/SUP], Morales-Nebreda L[SUP]1[/SUP], Perlman H[SUP]1[/SUP], Ceco E[SUP]1[/SUP], Lecuona E[SUP]1[/SUP], Dada LA[SUP]1[/SUP], Misharin AV[SUP]1[/SUP], Mutlu GM[SUP]3[/SUP], Sznajder JI[SUP]4[/SUP], Budinger GRS[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+/-[/SUP] and atrogin-1[SUP]-/-[/SUP] 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.
PMID: 30530483 DOI: 10.4049/jimmunol.1701433
[h=1]Influenza A Virus Infection Induces Muscle Wasting via IL-6 Regulation of the E3 Ubiquitin Ligase Atrogin-1.[/h] Radigan KA[SUP]1[/SUP], Nicholson TT[SUP]1[/SUP], Welch LC[SUP]1[/SUP], Chi M[SUP]1[/SUP], Amarelle L[SUP]1,[/SUP][SUP]2[/SUP], Angulo M[SUP]1,[/SUP][SUP]2[/SUP], Shigemura M[SUP]1[/SUP], Shigemura A[SUP]1[/SUP], Runyan CE[SUP]1[/SUP], Morales-Nebreda L[SUP]1[/SUP], Perlman H[SUP]1[/SUP], Ceco E[SUP]1[/SUP], Lecuona E[SUP]1[/SUP], Dada LA[SUP]1[/SUP], Misharin AV[SUP]1[/SUP], Mutlu GM[SUP]3[/SUP], Sznajder JI[SUP]4[/SUP], Budinger GRS[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+/-[/SUP] and atrogin-1[SUP]-/-[/SUP] 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.
PMID: 30530483 DOI: 10.4049/jimmunol.1701433