Last Updated: 07/07/2025
Mechanism of Action of Lipoxin in Protecting the Development of Experimental Cerebral Malaria
Objectives
This project aims to understand the mechanisms involved in protecting the development of CM by lipoxin, in addition to determining its potential use as adjuvant therapy, in association with antimalarials, in the treatment of severe malaria.
Malaria, caused by the protozoan parasite Plasmodium, is still a serious public health problem in the world, causing more than half a million fatalities each year. One of the aspects related to this fact is the poor understanding of parasite-host interactions. In this context, cerebral malaria (CM) is an often lethal neurovascular syndrome, caused mainly by infection with Plasmodium falciparum. Even with efficient antimalarial treatment, 10-20% of patients succumb to infection, so adjuvant therapies that act on important targets involved in the pathogenesis of the disease are urgently needed. Although the pathogenesis of CM is complex and not fully understood, observations in animal models (experimental cerebral malaria – ECM) and in humans infected with P. falciparum support the hypothesis that it is multifactorial, involving the accumulation of infected erythrocytes and leukocytes in the cerebral microvasculature, and exacerbated production of pro-inflammatory cytokines such as IFN-³, TNF- ±, lymphotoxin- ± and IL-12. However, the use of knockouts for various pro-inflammatory cytokines has not demonstrated a protective effect, suggesting a redundancy between these mediators. Preliminary results indicate that lipoxin, an anti-inflammatory mediator derived from arachidonic acid metabolism by 5-lipoxygenase, is able to protect mice against ECM. In addition, lipoxin prolongs survival and reduces the proinflammatory response in wild mice (WT) infected with Plasmodium.
Dec 2016 — Nov 2018
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