Systemic interleukin-6 inhibition ameliorates acute neuropsychiatric phenotypes in a murine model of acute lung injury

• DOI: 10.1186/s13054-022-04159-x
• Publication Date: 2022-09-13T09:03:18Z
• Authors: Faizan Anwar; Nicklaus A. Sparrow; Mohammad Harun Ra...; Gena Guidry; Michael M. Gezalian; Eric J. Ley; Maya Koronyo-Hamaoui; Itai Danovitch; E. Wesley Ely; S. Ananth Karumanchi; Shouri Lahiri
• Keywords: IL-6; VILI; RC86-88.9; Interleukin-6; Research; Ventilator-Induced Lung Injury; Acute Lung Injury; Delirium; Medical emergencies. Critical care. Intensive care. First aid; Anxiety; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Neural injury; Neuroinflammation; Animals

Abstract Acute neuropsychiatric impairments occur in over 70% of patients with acute lung injury. Mechanical ventilation is a well-known precipitant injury and strongly associated the development delirium anxiety phenotypes. In prior studies, we demonstrated that IL-6 mediates neuropathological changes frontal cortex hippocampus animals mechanical ventilation-induced brain injury; however, effect systemic inhibition on structural functional phenotypes not known. We hypothesized murine model (VILI) would induce neural to amygdala hippocampus, regions are implicated diverse conditions, corresponding delirium- anxiety-like impairments. Furthermore, these reverse inhibition. VILI was induced using high tidal volume (35 cc/kg) ventilation. Cleaved caspase-3 (CC3) expression quantified as marker found be significantly increased group compared spontaneously breathing or anesthetized mechanically ventilated mice 10 cc/kg volume. treated had reduced amygdalar hippocampal CC3 saline-treated amelioration behaviors open field, elevated plus maze, Y-maze tests. Overall, data provide evidence pathogenic role mediating symptoms preclinical justification assess potential intervention ameliorate following VILI.