IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury

• DOI: 10.1165/rcmb.2021-0072oc
• Publication Date: 2021-05-20T18:19:41Z
• Authors: Nicklaus A. Sparrow; Faizan Anwar; Ambart E. Covarru...; Padmesh S. Rajput; Mohammad Harun Ra...; Peyton L. Nisson; Michael M. Gezalian; Shahed Toossi; Maranatha O. Ayodele; S. Ananth Karumanchi; E. Wesley Ely; Shouri Lahiri
• Keywords: Inflammation; Neurons; 0301 basic medicine; Interleukin-6; Tumor Suppressor Proteins; Ventilator-Induced Lung Injury; Delirium; Apoptosis; Hippocampus; Antibodies; Frontal Lobe; 3. Good health; Repressor Proteins; Disease Models, Animal; Mice; 03 medical and health sciences; Animals; Female; HSP90 Heat-Shock Proteins; Proto-Oncogene Proteins c-fos

Mechanical ventilation is a known risk factor for delirium, cognitive impairment characterized by dysfunction of the frontal cortex and hippocampus. Although IL-6 upregulated in mechanical ventilation-induced lung injury (VILI) may contribute to it not whether inhibition systemic mitigates delirium-relevant neuropathology. To histologically define neuropathological effects an experimental VILI model, was simulated anesthetized adult mice using 35 cc/kg tidal volume model. There were two control groups, as follow: 1) spontaneously breathing or 2) mechanically ventilated with 10 distinguish anesthesia from VILI. Two hours before inducing VILI, treated either anti-IL-6 antibody, receptor saline. Neuronal injury, stress, inflammation assessed immunohistochemistry. CC3 (cleaved caspase-3), neuronal apoptosis marker, significantly increased (P < 0.001) hippocampal 0.0001) brain regions accompanied significant increases c-Fos heat shock protein-90 cortices compared 0.001). These findings related cerebral hypoxia, there no evidence irreversible death. Frontal reduced antibody 0.01 P 0.0001, respectively) 0.05 saline mice. In summary, induces potentially reversible hippocampus, which mitigated inhibition. data suggest novel neuroprotective role that justifies further investigation.