Susceptibility to Plasmodium berghei infection in rats is modulated by the acute phase response.

Brown Norway (BN) and Sprague Dawley (SD) rats are known to differ in their susceptibility to infection with sporozoites of Plasmodium berghei, as measured by the density of liver schizonts. Because of the known inhibitory effect of non-specific immunomodulators on schizont development, we compared some aspects of the acute phase response in these two rat strains. LPS induced IL-6 production was measured in supernatants of spleen cells and peritoneal macrophages of both strains. SD rats, which are the least susceptible to P. berghei sporozoites, showed significantly higher IL-6 production by macrophages from both sources. When LPS was administered in vivo, SD rats also had a significantly higher IL-6 response. Hepatocytes from both strains were cultured in the presence of IL-6. After three days of culture, alpha 2-Macroglobulin concentrations in the supernatants of SD hepatocytes were much higher than those from BN rats. Kupffer cell depletion in both BN and SD rats was correlated with a significant increase in liver schizont density, but did not abrogate the difference in susceptibility. From these results we conclude that the higher cytokine production capacity of SD rats compared to BN rats, may contribute to the difference in susceptibility to P. berghei sporozoites between these strains, but that other yet unknown factors are also involved.

Inhibition of Plasmodium berghei liver schizont development and reduction of cytokine production capacity in rats by dietary fish oil supplementation.

Experimental primary infection with Plasmodium berghei in rats is known to be influenced by several cytokines. Dietary supplementation of n-3 fatty acids has been shown to influence cytokine production capacity and to protect mice from cerebral malaria. We investigated the effect of dietary fish oil (FO) supplementation on cytokine and nitric oxide production and liver schizont development in male brown Norway rats. Control groups were fed either a corn oil-supplemented diet (CO) or standard lab chow (LC). After six weeks on either diet, rats given supplementary FO had a significantly lower production of interleukin-1 (IL-1) and IL-6 after stimulation with lipopolysaccharide, and also had significantly lower numbers of liver schizonts compared with CO- or LC-fed animals. We conclude that in rats, an FO-supplemented diet reduces the production capacity of IL-1 and IL-6 and inhibits schizont development after intravenous inoculation of P. berghei sporozoites. Fish oil did not influence nitric oxide production by peritoneal macrophages.

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

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.