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Tissue distribution of migration inhibitory factor and inducible nitric oxide synthase in falciparum malaria and sepsis in African children

Clark, Ian A; Awburn, Melissa M; Whitten, Richard O; Harper, Clive G; Liomba, N George; Molyneux, Malcolm E and Taylor, Terrie E (2003) Tissue distribution of migration inhibitory factor and inducible nitric oxide synthase in falciparum malaria and sepsis in African children. Malaria Journal, 2 . Article Number: 6. ISSN 1475-2875

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Official URL: http://www.malariajournal.com/content/2/1/6

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Abstract

Background: The inflammatory nature of falciparum malaria has been acknowledged since increased circulating levels of tumour necrosis factor (TNF) were first measured, but precisely where the mediators downstream from this prototype inflammatory mediator are generated has not been investigated. Here we report on the cellular distribution, by immunohistochemistry, of migration inhibitory factor (MIF) and inducible nitric oxide synthase (iNOS) in this disease, and in sepsis. Methods: We stained for MIF and iNOS in tissues collected during 44 paediatric autopsies in Blantyre, Malawi. These comprised 42 acutely ill comatose patients, 32 of whom were diagnosed clinically as cerebral malaria and the other 10 as non-malarial diseases. Another 2 were nonmalarial, non-comatose deaths. Other control tissues were from Australian adults. Results: Of the 32 clinically diagnosed cerebral malaria cases, 11 had negligible histological change in the brain, and no or scanty intravascular sequestration of parasitised erythrocytes, another 7 had no histological changes in the brain, but sequestered parasitised erythrocytes were present (usually dense), and the remaining 14 brains showed micro-haemorrhages and intravascular mononuclear cell accumulations, plus sequestered parasitised erythrocytes. The vascular walls of the latter group stained most strongly for iNOS. Vascular wall iNOS staining was usually of low intensity in the second group (7 brains) and was virtually absent from the cerebral vascular walls of 8 of the 10 comatose patients without malaria, and also from control brains. The chest wall was chosen as a typical non-cerebral site encompassing a range of tissues of interest. Here pronounced iNOS staining in vascular wall and skeletal muscle was present in some 50% of the children in all groups, including septic meningitis, irrespective of the degree of staining in cerebral vascular walls. Parasites or malarial pigment were rare to absent in all chest wall sections. While MIF was common in chest wall vessels, usually in association with iNOS, it was absent in brain vessels. Conclusions: These results agree with the view that clinically diagnosed cerebral malaria in African children is a collection of overlapping syndromes acting through different organ systems, with several mechanisms, not necessarily associated with cerebral vascular inflammation and damage, combining to cause death. Ian A Clark*1, Melissa M Awburn1, Richard O Whitten2, Clive G Harper3, N George Liomba4, Malcolm E Molyneux5,6 and Terrie E Taylor6,7

Item Type:Article
Additional Information:Published: 8 April 2003. 7 pages (page numbers not for citation purposes).
Uncontrolled Keywords:TUMOR-NECROSIS-FACTOR; HUMAN CEREBRAL MALARIA; SEPTIC SHOCK; FACTOR MIF; GENE-EXPRESSION; FACTOR-ALPHA; BLOOD-FLOW; MACROPHAGE; CYTOKINE; DISEASE
Subjects:R Medicine > R Medicine (General)
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Liverpool School of Tropical Medicine
DOI:10.1186/1475-2875-2-6
Publisher's Statement:© 2003 Clark et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. This article is available from: http://www.malariajournal.com/content/2/1/6
Related URLs:
Refereed:Yes
Status:Published
ID Code:787
Deposited On:11 Jul 2008 15:28
Last Modified:19 May 2011 20:14

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