Cytokines and adhesion molecules expression in the brain in human cerebral malaria.
Although the role of systemic proinflammatory cytokines, IL-1beta and TNF-alpha, and their up-regulation of adhesion molecules, ICAM-1, VCAM-1 and E-Selectin, in the pathogenesis of cerebral malaria (CM) is well established, the role of local cytokine release remain unclear. Immunohistochemistry (IHC) was used to compare the expression of ICAM-1, VCAM-1, E-Selectin, IL-1beta, TNF-a and TGF-beta at light microscopic level in cerebral, cerebellar and brainstem postmortem cryostat sections from 10 CM, 5 severe malarial anemia (SMA), 1 purulent bacterial meningitis (PBM), 2 non-central nervous system infections (NCNSI) and 3 non-infections (NI) deaths in Ghanaian children. Fatal malaria and Salmonella sepsis showed significantly higher vascular expression of all 3 adhesion molecules, with highly significant co-localization with sequestration in the malaria cases. However, there was negligible difference between CM and SMA. TGF-beta showed intravascular and perivascular distribution in all cases, but expression was most intense in the PBM case and CM group. TNF-alpha and IL-1beta showed prominent brain parenchymal staining, in addition to intravascular and perivascular staining, in only the PBM case and CM group. The maximal expression of all 6 antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation is a feature of fatal malaria and Salmonella sepsis, with adhesion molecule expression being highly correlated with sequestration. IL-1beta and TNF-alpha are upregulated in only cases with neurodegenerative lesions, whilst TGF-beta is present in all cases. Both cytokines and adhesion molecules were maximally upregulated in the cerebellar sections of the malaria cases.
Armah
Henry
H
Department of Pathology, University of Ghana Medical School, Accra, Ghana.
Wired
Edwin Kwame
EK
Dodoo
Alfred Kofi
AK
Adjei
Andrew Anthony
AA
Tettey
Yao
Y
Gyasi
Richard
R
D001933:Brain Stem / Q000276:immunology / Q000378:metabolism; D002531:Cerebellum / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019040:E-Selectin / Q000032:analysis; D005260:Female; D005869:Ghana; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis*; D016779:Malaria, Cerebral / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D013687:Telencephalon / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D019040:E-Selectin; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1