Cytokine profile suggesting that murine cerebral malaria is an encephalitis

Abstract

Cerebral malaria (CM) remains a poorly understood and life-threatening complication of malaria caused by the parasite Plasmodium falciparum. The discovery that murine CM caused by Plasmodium berghei ANKA and human CM are both characterized by production of inflammatory cytokines, especially tumor necrosis factor alpha (TNF-␣), led to a revival of the suggestion that P. berghei CM may have value as a model of the human disease. In this study, quantitative reverse transcription-PCR was used to measure levels of message for 18S rRNA of P. berghei and 10 cytokines in the brains, livers, and spleens of mice during the induction and course of CM. A coordinated increase in RNA of parasite and proinflammatory cytokines was observed in the brains of mice in parallel with onset of CM. Levels of message for parasite, TNF-␣, and gamma interferon increased in the brains of mice from day 5 to death on day 7. These changes were observed only in the brain, and message for other cytokines remained near baseline levels. This demonstrated that parasite sequestration does take place in the brains of mice with CM. Histologically, CM was characterized by widespread damage to the microvasculature in the brain with focal infiltration of inflammatory cells. The pattern of cytokine production in the brain is characteristic of other murine encephalitides.

Involvement of IFN-γ receptor-mediated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection

“…This also explains the smaller amounts of TNF- § transcripts in the brains of KO mice ( Table 2). Our results are in agreement with those of previous studies [31][32][33] showing a correlation between IFN-+ and TNF- § transcripts, and TNF- § protein and the pathogenesis of ECM. The synthesis of TNF- § by infected KO mice also suggests that TNF- § may be released in response to stimuli other than IFN-+ .…”

Behavioural and histopathological alterations in mice with cerebral malaria

“…Brain tissue not directly involved by haemorrhages showed cerebral oedema and, in some mice, damage of neurones and glia with pycnotic nuclei and increased cytoplasmic eosinophilia, compatible with ischaemic-hypoxic cell damage. Notably, these histological changes are similar to those that have been described previously [8,11,17,39]. However, the significance of these histological alterations in the pathogenesis of CM remains uncertain and requires further studies [40,41].…”

Pro-inflammatory cytokines predominate in the brains of dogs with visceral leishmaniasis: A natural model of neuroinflammation during systemic parasitic infection

“…Astrocytes infected with Toxoplasma gondii produced IL-1␤, IL-6 and GM-CSF, while microglia produced TNF-␣ and TGF-␤ concomitantly (Fischer et al, 1997). In murine cerebral malaria, increased IL-1␤, IFN-␥ and TNF-␣ gene expression have been reported, but no alterations in IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 or GM-CSF have been described (Jennings et al, 1997). Further, cerebral-malaria-susceptible mice expressed lower levels of IL-10 in the brain (Kossodo et al, 1997), and in human cases of cerebral malaria, high immunohistochemical detection of TGF-␤1, 2 and 3 has been observed (Deininger et al, 2000).…”