Interleukin 10 protects the brain microcirculation from spirochetal injury.

Abstract

Spirochetal infections are an important cause of neurological disease. In previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with Borrelia turicatae, an agent of tick-borne relapsing fever in North America, developed mild meningitis and parenchymal activation/infiltration by interleukin 10 (IL-10)-producing microglia/macrophages. Here, we investigated the neuroprotective effects of IL-10 during spirochetal infection by comparing the outcomes of B. turicatae infection in wild-type and IL-10-deficient RAG2-deficient mice. Mice were infected with either serotype 1 (Bt1), which causes more brain infection but lower bacteremia, or Bt2, which causes less brain infection but higher bacteremia. Interleukin 10 deficiency resulted in early death from subarachnoid/intraparenchymal brain hemorrhage in Bt2-infected mice. These mice had marked apoptosis of brain microvascular endothelial cells as assessed by terminal transferase-mediated DNA nick end-labeling staining. In contrast, Bt1 infection caused milder subarachnoid hemorrhage. Neuronal apoptosis was observed in mice infected with both serotypes and was prominent in the cerebellum. Neutralization of tumor necrosis factor prevented death and reduced morbidity and brain injury in mice infected by both serotypes. We conclude that IL-10 plays a critical role protecting the cerebral microcirculation from spirochetal injury possibly by inhibition effects of tumor necrosis factor.

• Authors: Diana Londoño, Jenny Carvajal, Carolina Arguelles-Grande, Adriana Marques, Diego Cadavid
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 67 Issue 10 Pg. 976-83 (Oct 2008) ISSN: 0022-3069 [Print] England
• PMID: 18800010 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Coloring Agents
• Cytokines
• Tumor Necrosis Factor Inhibitors
• Interleukin-10

Topics

• Animals
• Borrelia Infections (mortality, pathology, prevention & control)
• Brain (pathology)
• Coloring Agents
• Cytokines (biosynthesis, genetics)
• Female
• Hemorrhage (etiology, pathology)
• In Situ Nick-End Labeling
• Interleukin-10 (genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microcirculation (pathology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor Inhibitors