Info Coronavirus (EUA)

Study Sheds Light on Immune Mechanism Which Triggers Cytokine Storm Typical of COVID-19

Publicado em 01 dezembro 2020

The study reveals a novel mechanistic link between NE expression in atherosclerotic plaques and concomitant pro-inflammatory bioactive IL-1ß secretion from ECs which could reveal additional potential anti-IL-1ß therapeutic targets and provide further insights into the inflammatory process by which vascular disease develops. Researchers investigated neutrophil elastase (NE), a potent serine protease detected in vulnerable areas of human carotid plaques, as a potential “trigger” for IL-1ß processing and release. According to the authors, the findings support the use of inflammasome activation both as a marker of disease prognosis, helping medical teams identify high-risk patients at an early stage, and as a potential therapeutic target in severe COVID-19.

“Drugs already approved for human use are capable of inhibiting inflammasome activation. These drugs can now be tested in the context of infection by SARS-CoV-2,” Dario Zamboni, a professor at USP’s Ribeirão Preto Medical School (FMRP-USP) and principal investigator for the study, told Agência FAPESP.

“The response to various pathogens involves inflammasome activation, and most of the time this blocks the infection and protects the organism. However, in some COVID-19 patients, the defense system appears to be overactivated, and we’re now trying to understand why this happens,” Zamboni said. The involvement of this immune mechanism in the systemic inflammation that is characteristic of severe COVID-19 has been studied by scientists in several countries over the past few months. The Ribeirão Preto group is the first to demonstrate the activation of a specific type of inflammasome in response to infection by SARS-CoV-2 in patients.

“We’re looking for other drugs capable of inhibiting the NLRP3 inflammasome for testing in a clinical trial,” Zamboni said. “As we discover more about inflammasome activation mechanisms in COVID-19, we can identify drugs that reduce the inflammatory process more effectively.”