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IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury.
Sparrow, Nicklaus A; Anwar, Faizan; Covarrubias, Ambart E; Rajput, Padmesh S; Rashid, Mohammad Harun; Nisson, Peyton L; Gezalian, Michael M; Toossi, Shahed; Ayodele, Maranatha O; Karumanchi, S Ananth; Ely, E Wesley; Lahiri, Shouri.
  • Sparrow NA; Department of Neurology.
  • Anwar F; Department of Neurology.
  • Covarrubias AE; Department of Medicine.
  • Rajput PS; Department of Neurology.
  • Rashid MH; Department of Neurosurgery.
  • Nisson PL; Department of Neurosurgery.
  • Gezalian MM; Department of Neurosurgery.
  • Toossi S; Department of Neurology, and.
  • Ayodele MO; Department of Neurosurgery.
  • Karumanchi SA; Department of Neurology, and.
  • Ely EW; Department of Neurosurgery.
  • Lahiri S; Department of Neurology, and.
Am J Respir Cell Mol Biol ; 65(4): 403-412, 2021 10.
Article in English | MEDLINE | ID: covidwho-1237350
Semantic information from SemMedBD (by NLM)
1. interleukin-6 AUGMENTS Lung Injury
Subject
interleukin-6
Predicate
AUGMENTS
Object
Lung Injury
2. frontal lobe LOCATION_OF Proto-Oncogene Proteins c-fos|FOS
Subject
frontal lobe
Predicate
LOCATION_OF
Object
Proto-Oncogene Proteins c-fos|FOS
3. frontal lobe LOCATION_OF HSP90 Heat-Shock Proteins
Subject
frontal lobe
Predicate
LOCATION_OF
Object
HSP90 Heat-Shock Proteins
4. Apoptosis Marker STIMULATES Proto-Oncogene Proteins c-fos|FOS
Subject
Apoptosis Marker
Predicate
STIMULATES
Object
Proto-Oncogene Proteins c-fos|FOS
5. Apoptosis Marker STIMULATES HSP90 Heat-Shock Proteins
Subject
Apoptosis Marker
Predicate
STIMULATES
Object
HSP90 Heat-Shock Proteins
6. frontal lobe PART_OF Mus
Subject
frontal lobe
Predicate
PART_OF
Object
Mus
7. frontal lobe LOCATION_OF Inflammation
Subject
frontal lobe
Predicate
LOCATION_OF
Object
Inflammation
8. interleukin-6 DISRUPTS Inflammation
Subject
interleukin-6
Predicate
DISRUPTS
Object
Inflammation
9. interleukin-6 AUGMENTS Lung Injury
Subject
interleukin-6
Predicate
AUGMENTS
Object
Lung Injury
10. frontal lobe LOCATION_OF Proto-Oncogene Proteins c-fos|FOS
Subject
frontal lobe
Predicate
LOCATION_OF
Object
Proto-Oncogene Proteins c-fos|FOS
11. frontal lobe LOCATION_OF HSP90 Heat-Shock Proteins
Subject
frontal lobe
Predicate
LOCATION_OF
Object
HSP90 Heat-Shock Proteins
12. Apoptosis Marker STIMULATES Proto-Oncogene Proteins c-fos|FOS
Subject
Apoptosis Marker
Predicate
STIMULATES
Object
Proto-Oncogene Proteins c-fos|FOS
13. Apoptosis Marker STIMULATES HSP90 Heat-Shock Proteins
Subject
Apoptosis Marker
Predicate
STIMULATES
Object
HSP90 Heat-Shock Proteins
14. frontal lobe PART_OF Mus
Subject
frontal lobe
Predicate
PART_OF
Object
Mus
15. frontal lobe LOCATION_OF Inflammation
Subject
frontal lobe
Predicate
LOCATION_OF
Object
Inflammation
16. interleukin-6 DISRUPTS Inflammation
Subject
interleukin-6
Predicate
DISRUPTS
Object
Inflammation
ABSTRACT
Mechanical ventilation is a known risk factor for delirium, a cognitive impairment characterized by dysfunction of the frontal cortex and hippocampus. Although IL-6 is upregulated in mechanical ventilation-induced lung injury (VILI) and may contribute to delirium, it is not known whether the inhibition of systemic IL-6 mitigates delirium-relevant neuropathology. To histologically define neuropathological effects of IL-6 inhibition in an experimental VILI model, VILI was simulated in anesthetized adult mice using a 35 cc/kg tidal volume mechanical ventilation model. There were two control groups, as follow 1) spontaneously breathing or 2) anesthetized and mechanically ventilated with 10 cc/kg tidal volume to distinguish effects of anesthesia from VILI. Two hours before inducing VILI, mice were treated with either anti-IL-6 antibody, anti-IL-6 receptor antibody, or saline. Neuronal injury, stress, and inflammation were assessed using immunohistochemistry. CC3 (cleaved caspase-3), a neuronal apoptosis marker, was significantly increased in the frontal (P < 0.001) and hippocampal (P < 0.0001) brain regions and accompanied by significant increases in c-Fos and heat shock protein-90 in the frontal cortices of VILI mice compared with control mice (P < 0.001). These findings were not related to cerebral hypoxia, and there was no evidence of irreversible neuronal death. Frontal and hippocampal neuronal CC3 were significantly reduced with anti-IL-6 antibody (P < 0.01 and P < 0.0001, respectively) and anti-IL-6 receptor antibody (P < 0.05 and P < 0.0001, respectively) compared with saline VILI mice. In summary, VILI induces potentially reversible neuronal injury and inflammation in the frontal cortex and hippocampus, which is mitigated with systemic IL-6 inhibition. These data suggest a potentially novel neuroprotective role of systemic IL-6 inhibition that justifies further investigation.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-6 / Apoptosis / Delirium / Ventilator-Induced Lung Injury / Antibodies / Neurons Type of study: Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Animals Language: English Journal: Am J Respir Cell Mol Biol Journal subject: Molecular Biology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-6 / Apoptosis / Delirium / Ventilator-Induced Lung Injury / Antibodies / Neurons Type of study: Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Animals Language: English Journal: Am J Respir Cell Mol Biol Journal subject: Molecular Biology Year: 2021 Document Type: Article