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Migration inhibitory factor in the cerebral and systemic endothelium in sepsis and malaria

Ian Clark1, Melissa Awburn

  • 1School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australia.

Critical Care Medicine
|May 11, 2002
PubMed
Abstract

Insights

Migration inhibitory factor (MIF) is absent in brain blood vessels during pediatric sepsis and malaria, unlike other inflammatory mediators. This suggests reduced anti-inflammatory activity in the brain, potentially impacting disease severity.

Area of Science:

  • Immunology
  • Pathology
  • Pediatric Infectious Diseases

Background:

  • Inflammatory mediators play a crucial role in severe infections like falciparum malaria and sepsis.
  • Inducible nitric oxide synthase (iNOS) expression is observed to be lower in the cerebral vasculature compared to the systemic vasculature in African children.
  • Migration inhibitory factor (MIF) is a key inflammatory mediator with potential roles in regulating immune responses and glucocorticoid activity.

Purpose of the Study:

  • To investigate the presence and distribution of MIF in the vasculature of African children with sepsis and falciparum malaria.
  • To compare MIF expression in the cerebral vasculature with that in the systemic vasculature.
  • To determine if MIF levels correlate with the observed differences in iNOS induction between cerebral and systemic vasculature.

Main Methods:

  • Immunohistochemical analysis of tissue samples from the blood vessel walls of the brain and axillary space.
  • Comparison of samples from autopsies of African children with sepsis and falciparum malaria.
  • Inclusion of control tissues from non-infectious causes of death and internal positive staining controls for MIF and iNOS.

Main Results:

  • Intense MIF staining was detected in endothelial cells of axillary vessels in sepsis and most malaria cases, mirroring iNOS staining patterns.
  • MIF was not detected in vascular endothelial cells within the brain, where iNOS staining was less intense.
  • Control tissues showed minimal or no staining for MIF, while ependymal and glial cells in the brains served as positive controls for both MIF and iNOS.

Conclusions:

  • Endothelial cells are a significant site of inflammatory mediator activity in sepsis and malaria.
  • The lower presence of MIF in the brain's vasculature may indicate reduced suppression of anti-inflammatory glucocorticoids in the central nervous system.
  • The absence of MIF in cerebral vasculature endothelial cells could be linked to the lack of thrombomodulin in these cells, warranting further investigation into the systemic distribution of MIF in inflammatory states.

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