Cytokines inhibit the development of liver schizonts of the malaria parasite plasmodium berghei in vivo

Abstract

The effect of induction of an acute‐phase response and its mediators on the development of liver schizonts of the rodent malaria parasite Plasmodium berghei was investigated in Brown Norway rats. Subcutaneous injection of turpentine oil 24 h or 5 min before inoculation of sporozoites resulted in 80% and 35% reduction of schizont development, respectively. Turpentine oil induced high plasma levels of interleukin‐6 (IL‐6). Intraperitoneal administration of IL‐1, IL‐6 or both, significantly reduced liver schizont development. This reduction was also present if IL‐6 had been administered 24 h after sporozoite inoculation. Inhibition induced by IL‐1 could be prevented by simultaneous administration of polyclonal anti‐IL‐6. Administration of polyclonal anti‐IL‐6 without IL‐1 resulted in a 40% increase of liver schizonts compared to control animals. We conclude that induction of an acute‐phase response during experimental Plasmodium berghei infections in Brown Norway rats, strongly inhibits liver schizont development and that IL‐6 is a key mediator in this process.