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

Armah H, Wired EK, Dodoo AK, Adjei AA, Tettey Y, Gyasi R - Int J Environ Res Public Health (2005)

Bottom Line: 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.IL-1beta and TNF-alpha are upregulated in only cases with neurodegenerative lesions, whilst TGF-beta is present in all cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Ghana Medical School, Accra, Ghana.

ABSTRACT
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.

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(original magnification, X100): Immunohistology for TGFβ, IL-1β & TNFα. (A–B) TGFβ staining (intravascular & perivascular). (A) NCNSI section: moderate in some fields (average score +). (A) CM/PBM section: strong in all fields (average score +++). (C–E) IL-1β staining (intravascular, perivascular & parenchymal). (C) PBM section: moderate in some fields (average score +). (D) CM section: strong in all fields (average score +++). (E) NCNSI section: no staining in all fields (average score −). TNFα staining (intravascular, perivascular & parenchymal). CM/PBM section: strong in all fields (average score +++).
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f2-ijerph-02-00123: (original magnification, X100): Immunohistology for TGFβ, IL-1β & TNFα. (A–B) TGFβ staining (intravascular & perivascular). (A) NCNSI section: moderate in some fields (average score +). (A) CM/PBM section: strong in all fields (average score +++). (C–E) IL-1β staining (intravascular, perivascular & parenchymal). (C) PBM section: moderate in some fields (average score +). (D) CM section: strong in all fields (average score +++). (E) NCNSI section: no staining in all fields (average score −). TNFα staining (intravascular, perivascular & parenchymal). CM/PBM section: strong in all fields (average score +++).

Mentions: Positive immunostaining for TGF-β showed intravascular and perivascular distribution (Figures 2A & 2B), whilst there was intravascular, perivascular and prominent brain parenchymal staining for IL-1β (Figures 2C–E) and TNF-α (Figures 2F). TGF-β was detected in intravascular and perivascular distribution in brain tissue from all 5 groups studied, but expression was more intense in PBM and CM groups (Figures 2A & 2B). TGF-β showed moderate intravascular and perivascular immunostaining in some fields (average score of +) of all the NCNSI sections (Figure 2A), whilst it’s staining was strong in intravascular and perivascular locations in all fields (average score of +++) of all the CM and PBM sections (Figure 2B).


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

Armah H, Wired EK, Dodoo AK, Adjei AA, Tettey Y, Gyasi R - Int J Environ Res Public Health (2005)

(original magnification, X100): Immunohistology for TGFβ, IL-1β & TNFα. (A–B) TGFβ staining (intravascular & perivascular). (A) NCNSI section: moderate in some fields (average score +). (A) CM/PBM section: strong in all fields (average score +++). (C–E) IL-1β staining (intravascular, perivascular & parenchymal). (C) PBM section: moderate in some fields (average score +). (D) CM section: strong in all fields (average score +++). (E) NCNSI section: no staining in all fields (average score −). TNFα staining (intravascular, perivascular & parenchymal). CM/PBM section: strong in all fields (average score +++).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3814706&req=5

f2-ijerph-02-00123: (original magnification, X100): Immunohistology for TGFβ, IL-1β & TNFα. (A–B) TGFβ staining (intravascular & perivascular). (A) NCNSI section: moderate in some fields (average score +). (A) CM/PBM section: strong in all fields (average score +++). (C–E) IL-1β staining (intravascular, perivascular & parenchymal). (C) PBM section: moderate in some fields (average score +). (D) CM section: strong in all fields (average score +++). (E) NCNSI section: no staining in all fields (average score −). TNFα staining (intravascular, perivascular & parenchymal). CM/PBM section: strong in all fields (average score +++).
Mentions: Positive immunostaining for TGF-β showed intravascular and perivascular distribution (Figures 2A & 2B), whilst there was intravascular, perivascular and prominent brain parenchymal staining for IL-1β (Figures 2C–E) and TNF-α (Figures 2F). TGF-β was detected in intravascular and perivascular distribution in brain tissue from all 5 groups studied, but expression was more intense in PBM and CM groups (Figures 2A & 2B). TGF-β showed moderate intravascular and perivascular immunostaining in some fields (average score of +) of all the NCNSI sections (Figure 2A), whilst it’s staining was strong in intravascular and perivascular locations in all fields (average score of +++) of all the CM and PBM sections (Figure 2B).

Bottom Line: 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.IL-1beta and TNF-alpha are upregulated in only cases with neurodegenerative lesions, whilst TGF-beta is present in all cases.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Ghana Medical School, Accra, Ghana.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus