Cytokines and adhesion molecules expression in the brain in human cerebral malaria

Henry Armah1, Edwin Kwame Wired, Alfred Kofi Dodoo

  • 1Department of Pathology, University of Ghana Medical School, Accra, Ghana.

Insights

In fatal malaria, local brain inflammation involves specific cytokines and adhesion molecules, particularly in the cerebellum. These markers are also elevated in Salmonella sepsis, indicating shared pathways in severe infections.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Systemic cytokines like IL-1beta and TNF-alpha, and adhesion molecules (ICAM-1, VCAM-1, E-Selectin) are implicated in cerebral malaria (CM).
  • The role of local cytokine release in CM pathogenesis remains less understood.

Purpose of the Study:

  • To compare the expression of adhesion molecules and cytokines (IL-1beta, TNF-alpha, TGF-beta) in postmortem brain tissues from children with CM and other conditions.
  • To investigate the localization and correlation of these markers with disease severity and specific brain regions.

Main Methods:

  • Immunohistochemistry (IHC) was used on postmortem cryostat sections from Ghanaian children.
  • Examined tissues included cerebral, cerebellar, and brainstem regions from cases of CM, severe malarial anemia (SMA), bacterial meningitis (PBM), other infections (NCNSI), and non-infections (NI).

Main Results:

  • Fatal malaria and Salmonella sepsis showed significantly higher vascular expression of all three adhesion molecules, correlating with sequestration in malaria cases.
  • IL-1beta and TNF-alpha were prominently expressed in brain parenchyma only in PBM and CM cases, suggesting a link to neurodegenerative lesions.
  • TGF-beta was present in all cases, with highest intensity in PBM and CM groups.
  • Maximal expression of all studied antigens occurred in cerebellar sections of malaria cases.

Conclusions:

  • Endothelial activation, marked by adhesion molecule expression, is a feature of fatal malaria and Salmonella sepsis.
  • Local IL-1beta and TNF-alpha upregulation is associated with neurodegenerative lesions in CM.
  • Cerebellar regions show the highest upregulation of both cytokines and adhesion molecules in fatal malaria.

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