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IL‐10 protects the cerebral microcirculation from spirochetal injury
Author(s) -
Londoño Diana,
Marques Adriana,
Cadavid Diego
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a66-a
Subject(s) - neuroborreliosis , immunology , vasculitis , medicine , tumor necrosis factor alpha , inflammation , microcirculation , pathology , rag2 , interleukin , biology , cytokine , antibody , borrelia burgdorferi , disease , biochemistry , recombination , gene
The spirochetal infection relapsing fever (RF) can cause significant neurological complications referred to as neuroborreliosis. A study in RAG1 deficient mice, which are B and T cell deficient, found a strong correlation between suppression of disease and production of interleukin 10 (IL‐10) during persistent infection with the RF spirochete Borrelia turicatae (Bt). To confirm whether IL‐10 plays a protective role in RF we studied the outcome of persistent infection with serotype 2 (Bt2) in RAG2 deficient (RAG2−/−) mice in comparison with RAG2−/− mice also deficient in IL‐10 (IL‐10/RAG2−/−). The results showed that early after infection IL‐10/RAG2−/− mice but not RAG2−/− mice were moribund or died and exhibited brain hemorrhage and CNS vasculitis. The increase in the pro‐inflammatory cytokines TNF‐α and IL‐6 was much higher in IL‐10/RAG2−/− than in RAG2−/− mice. Neutralization of TNF‐α significantly improved survival and reduced but did not prevent brain hemorrhage or CNS vasculitis. In vitro Bt2 caused significant injury to brain microvascular endothelial cells (BMEC) that was not prevented by neutralization of TNF‐α. In contrast, exogenous IL‐10 decreased Bt2 injury to BMEC. We concluded that IL‐10 plays an important role protecting the cerebral microcirculation from spirochetal injury.