The cholinergic anti-inflammatory pathway alleviates acute lung injury.

The ubiquiotous nuclear protein HMGB1 is extracellularly released by dying cells or activated innate immunity cells to promote inflammation. Extracellular HMGB1 plays a prominent role in the pathogenesis of acute lung injury of infectious as well as sterile origin including hyperoxia. Excessive amounts of systemic HMGB1 and HMGB1-partner molecule complexes can be retained in the pulmonary circulation indicated by a substantial reduction of HMGB1 plasma levels in arterial versus venous blood. The cholinergic antiinflammatory mechanism ameliorates pulmonary inflammation by inhibiting HMGB1 release and HMGB1 receptor expression. This comprehension was recently reinforced by results reported in Molecular Medicine by Sitapara and coworkers demonstrating that administration of an α7 nicotinic acetylcholine receptor agonist attenuated hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation. Activating the cholinergic antiinflammatory path might be considered to alleviate severe COVID-19 with or without concurrent oxygen-induced lung injury.