Plasmodium berghei: Recombinant Interferon-γ and the Development of Parasitemia and Cerebral Lesions in Malaria-Infected Mice

Expression of proinflammatory cytokines in four regions of the brain in Macaque mulatta (rhesus) monkeys infected with Plasmodium coatneyi.

“…Sequestration of PRBC, the production of proinflammatory cytokines, and their downstream reactions such as mechanical blockage, aschemia, acidosis, hemorrhages, and nitric oxide production have been implicated in the pathogenesis. 6,[10][11][12][13][14][15][16] Murine studies using the Plasmodium berghei model support the role of TNF-␣, ICAM-1, and nitric oxide in the pathogenesis. [16][17][18][19] This model also reveals the importance of mechanical blockage in microvasculature damage.…”

“…6,[10][11][12][13][14][15][16] Murine studies using the Plasmodium berghei model support the role of TNF-␣, ICAM-1, and nitric oxide in the pathogenesis. [16][17][18][19] This model also reveals the importance of mechanical blockage in microvasculature damage. However, difficulty arises in extrapolating the underlying pathogenic mechanisms of human cerebral malaria from the murine findings, because the sequestration in humans involves PRBC rather than leukocytes and because the regulation of the cytokine network and nitric oxide production are fundamentally different between humans and mice.…”

“…7 These observations agree with previous conclusions based on pathologic studies of humans and murine models that implicate an overproduction of proinflammatory and TH-1 cytokines as an important factor in the immunopathogenesis of cerebral malaria. 7,[13][14][15][16][17][18]22 Results of this study indicate differences in local cytokine response in various regions of the brain after plasmodial infection. The proinflammatory cytokines (IL-1␤ and TNF-␣) and TH-1 cytokine (IFN-␥) had the highest levels of mRNA expression in the cerebellum during late P. coatneyi infection in rhesus monkeys.…”

Role of eicosanoids in the pathogenesis of murine cerebral malaria.

“…The increased expression of eicosanoid enzymes at day 7 of the infection coincided with the peak occurrence of cerebral malaria. [9][10][11] This increased production of phospholipase A2 and release of 5-lipoxygenase upon immune activation by malaria infection can result in the increased synthesis of leukotrienes and other hydroxy acids. Because the latter cause leukocyte adhesion and activation, increased vascular permeability, and production of proinflammatory cytokines, 15 it is likely that they will promote the pathogenesis of cerebral malaria.…”

“…8 The mechanisms involved in the induction of microvascular damage during cerebral malaria are not well studied. Because cerebral malaria is associated with the over-production of T helper-1 and proinflammatory cytokines (tumor necrosis factor-␣ [tnF-␣], interferon-␥ [IFN-␥], and interleukin-1 [IL-1]), [9][10][11] it is suggested that these cytokines cause cerebral malaria by up-regulation of intercellular adhesion molecule-1 (a cytoadhesion molecule involved in the adhesion of parasitized erythrocytes and mononuclear cells to endothelial cells) expression and nitric oxide production, which lead to mechanic blockage and disrupted neurotransmission. [11][12][13] However, whether endothelial blockage and activation themselves cause brain hemorrhage is not clear.…”