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Cytokines and Adhesion Molecules Expression in the Brain in Human Cerebral Malaria
Department of Pathology, University of Ghana Medical School
Department of Medical Laboratory Sciences, School of Allied Health Sciences
Histology & Electron Microscopy Unit, Noguchi Memorial Institute for Medical Research, University of Ghana College of Health Sciences, Accra, Ghana
* Author to whom correspondence should be addressed.
Received: 15 November 2004; Accepted: 6 February 2005 / Published: 30 April 2005
Abstract: Although the role of systemic proinflammatory cytokines, IL-1β and TNF-α, 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-1β, TNF-α and TGF- β 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-β showed intravascular and perivascular distribution in all cases, but expression was most intense in the PBM case and CM group. TNF-α and IL-1β 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-1β and TNF-α are upregulated in only cases with neurodegenerative lesions, whilst TGF-β is present in all cases. Both cytokines and adhesion molecules were maximally upregulated in the cerebellar sections of the malaria cases.
Keywords: Cytokines; Adhesion Molecules; Human Brain; Postmortem; Cerebral Malaria
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Armah, H.; Wiredu, E.K.; Dodoo, A.K.; Adjei, A.A.; Tettey, Y.; Gyasi, R. Cytokines and Adhesion Molecules Expression in the Brain in Human Cerebral Malaria. Int. J. Environ. Res. Public Health 2005, 2, 123-131.
Armah H, Wiredu EK, Dodoo AK, Adjei AA, Tettey Y, Gyasi R. Cytokines and Adhesion Molecules Expression in the Brain in Human Cerebral Malaria. International Journal of Environmental Research and Public Health. 2005; 2(1):123-131.
Armah, Henry; Wiredu, Edwin K.; Dodoo, Alfred K.; Adjei, Andrew A.; Tettey, Yao; Gyasi, Richard. 2005. "Cytokines and Adhesion Molecules Expression in the Brain in Human Cerebral Malaria." Int. J. Environ. Res. Public Health 2, no. 1: 123-131.