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

Objective: We have included migration inhibitory factor (MIF) in an ongoing immunohistochemical study comparing the site and intensity of the generation of inflammatory mediators in falciparum malaria, sepsis, and other causes of pediatric death in Africa. We wanted to determine whether it could account for our observation that inducible nitric oxide synthase is less strongly induced in the cerebral, compared with the systemic, vasculature. Data Sources: Comparisons of tissue samples taken from blood vessel walls from the brain and the axillary space in a series of sepsis and falciparum malaria autopsies of African children. Data Summary: Intense staining for MIF has been detected in endothelial cells of axillary region vessels of all sepsis cases and most of the malaria cases examined. This parallels our findings with inducible nitric oxide synthase staining. African and Western control tissues from noninfectious causes of death stained lightly or not at all. In contrast, MIF could not be detected in vascular endothelial cells within the brain, where inducible nitric oxide synthase staining was much less intense. Detection of both MIF and inducible nitric oxide synthase in ependymal and glial cells in the same brains served as an internal positive staining control. Conclusion: These outcomes add weight to the proposal that endothelial cells are a site of intense inflammatory mediator activity in sepsis and malaria. They also suggest that suppression of anti-inflammatory glucocorticoids by MIF may be lower in the brain than elsewhere in the body. The lack of MIF in cerebral vasculature endothelial cells may be linked to the absence of thrombomodulin in these cells. The systemic cellular distribution and intensity of MIF in human systemic inflammatory states has not been described.