The endocannabinoid system as a therapeutic target in the treatment of pathologies resulting from severe malaria

Malaria still kills thousands of people a year, mainly in the Americas and Africa. The death of people with malaria occurs due to the development of severe malaria, which, by WHO definition, goes beyond brain complications and includes lung, kidney and liver pathologies, which occur together or separately, resulting from infection by Plasmodium sp. As was recently observed for COVID-19, the severity of malaria is also due to an intense systemic inflammatory response that can affect these organs, leading to their dysfunction. It has already been shown that the presence of neutrophils in the lung during experimental malaria worsens lung dysfunction. Some studies in the literature have already shown that acting on the systemic inflammatory response can be a promising path to the patient’s rapid and effective recovery. In this sense, an alternative with anti-inflammatory action presents itself. The cannabinoid system is formed by CB1 and CB2 receptors, and their endogenous ligands anandamide and 2-arachidonoyl glycerol. Although the class of cannabinoids is widely known for their psychoactive effects, CB2 ligands have proven anti-inflammatory effects. The CB2 receptor is expressed on cells of the immune system and acts in the migration of cells in immunological responses, in the processing of antigen by macrophages and in the activation of T helper cells. Another highlight of the regulatory role of CB2 is the possibility of deactivating neutrophils, preventing their migration to the inflammatory site and the release of pro-inflammatory proteins. The research group has already shown that other G protein-linked receptors, such as FPR, have the potential to be therapeutic targets to control the exacerbated inflammatory response during severe malaria.

Basic Science

Jun 2022 — Jun 2024

Brazil