IL-1 alpha, promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria

Malaria causes hepatic inflammation and damage, which contribute to disease severity. The pro-inflammatory cytokine interleukin (IL)-1 alpha is released by non-hematopoietic or hematopoietic cells during liver injury. This study established the role of IL-1 alpha 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-1 alpha production. Systemically, IL-1 alpha deficiency attenuated weight loss and hypothermia but had minor effects on parasitemia control. In the liver, the absence of IL-1 alpha reduced the number ofTUNEL(+) cells and necrotic lesions. This finding was associated with a lower inflammatory response, including TNF-alpha. production. The main source of IL-1 alpha in the liver of infected mice was inflammatory cells, particularly neutrophils. The implication of IL-1 alpha 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. (AU)