Immunometabolic effect of nitric oxide on human macrophages challenged with the SARS-CoV2-induced cytokine storm

Acute bilateral pneumonia in individuals infected with COVID-19 is the result of a storm of pro-inflammatory cytokines and proteases intensively released by alveolar macrophages, recruiting neutrophils and promoting 'netosis'. Both processes are responsible for the subsequent damage (severe respiratory distress, neutropenia, leukopenia, humoral elevation of inflammation mediators, etc.), which spreads to other organs (thromboembolism, liver, kidney and heart damage). This proposal aims at the administration of inhaled nitric oxide (NO) and NO donors at the systemic level in order to prevent the activation of the innate immune system in the lung, as well as to avoid neutropenia and thromboembolism phenomena, preserving the adaptative immune system function for the benefit of the patient. For this purpose, the immunometabolic properties of human-derived macrophages treated with pro-inflammatory cytokines and an NO donor were evaluated. Overall design: mRNA profiles of primary cultures of human monocyte-derived macrophages treated with CK (IL1ß, IL-6, IL8, TNFa, IFN? and GM-CSF) 20ng/mL for 24h, DETANONOATE 500µM (D500µM) 24h or CK (1h)+DETANONOATE 500µM 24h (D500µM) in RPMI+2%FBS or vehicle (controls RPMI+2%FBS) **NOTE: the GSM7527763, GSM7527764 sample treatment information has been updated on Oct 13, 2024****