Breakdown of blood-brain barrier by virus-induced cytokine during Japanese encephalitis virus infection.
In this study we have shown, for the first time, that Japanese encephalitis virus (JEV) and a low molecular weight (10 kDa) macrophage-derived neutrophil chemotactic factor (MDF) produced following JEV infection in mice could cause an alteration in the permeability of the blood-brain barrier resulting in leakage of plasma protein bound Evans blue dye and radiolabelled erythrocytes in brain. The maximum leakage occurred at day 6 after intracerebral (i.c.) JEV infection and was sensitive to anti-JEV antisera. Further, MDF caused peak leakage of dye and radiolabelled erythrocytes at 1 h post inoculation with a decline thereafter. Complete restoration of the integrity of the blood-brain barrier occurred by the 4th hour. The extent of leakage was dose dependent and showed a direct correlation between the level of MDF, clinical sickness and virus titre in brain. Anti-MDF antisera protected the mice against the effects of MDF. These findings show that JEV-induced cytokine, MDF, alters the integrity of the blood-brain barrier and thus controls the cellular and plasma leakage into the CNS.
Mathur
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A
Postgraduate Department of Microbiology, K.G. Medical College, Lucknow, India.
Khanna
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N
Chaturvedi
U C
UC
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000473:pathology; D002630:Chemotactic Factors / Q000096:biosynthesis*; D004672:Encephalitis, Japanese / Q000378:metabolism* / Q000473:pathology; D007958:Leukocyte Count; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D013997:Time Factors
D002630:Chemotactic Factors