Abstract
Malaria causes hepatic inflammation and damage, which contribute to disease severity. The pro-inflammatory cytokine interleukin (IL)-1α is released by non-hematopoietic or hematopoietic cells during liver injury. This study established the role of IL-1α in the liver pathology caused by blood-stage P. chabaudi malaria. During acute infection, hepatic inflammation and necrosis were accompanied by NLRP3 inflammasome-independent IL-1α production. Systemically, IL-1α deficiency attenuated weight loss and hypothermia but had minor effects on parasitemia control. In the liver, the absence of IL-1α reduced the number of TUNEL+ cells and necrotic lesions. This finding was associated with a lower inflammatory response, including TNF-α production. The main source of IL-1α in the liver of infected mice was inflammatory cells, particularly neutrophils. The implication of IL-1α in liver inflammation and necrosis caused by P. chabaudi infection, as well as in weight loss and hypothermia, opens up new perspectives for improving malaria outcomes by inhibiting IL-1 signaling.
Highlights
Is a hallmark of malaria, which is a parasitic disease caused mainly by Plasmodium falciparum and Plasmodium vivax that results in almost half a million deaths per year[1]
To verify the production of IL-1α during hepatic necrosis and inflammation induced by bloodstage malaria, we first evaluated the serum concentration of the liver damage indicators enzymes aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH)
Damage and inflammation in the liver are common consequences of Plasmodium sp. infection that contribute to the development of severe malaria[35,36]
Summary
Is a hallmark of malaria, which is a parasitic disease caused mainly by Plasmodium falciparum and Plasmodium vivax that results in almost half a million deaths per year[1]. Hepatic inflammation is triggered in response to infection and tissue injury and is characterized by the recruitment of innate immune cells and the production of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1 and IL-613. IL-1α and IL-1β are important cytokines of the IL-1 family that induce fever, neutrophil influx and activation, monocyte recruitment, prostaglandin synthesis, T- and B-cell activation and cytokine production[14,15,16] These cytokines share the same receptor (IL-1R) but are different in the manner in which they are produced, released and exert their function. IL-1α, which leads to the rapid recruitment of inflammatory cells[18,19] Due to these characteristics, IL-1α is considered a damage-associated molecular pattern (DAMP), since it acts as an alarm signal to initiate inflammation in response to tissue injury[20].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
