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Effect of CCR5 receptor antagonist (MET-RANTES) on leukocyte-endothelium interactions in an experimental model of herpetic encephalitis


The Herpes Simplex Virus-1 (HSV-1) is responsible for several clinical manifestations in humans, including severe encephalitis. The aim of this study was to use Met-RANTES, a CCR1 and CCR5 antagonist, in the treatment of a severe model of HSV-1 encephalitis.


Wild type C57BL/6 mice were intracerebrally inoculated with 104 PFU of HSV-1 or PBS. Mice received Met-RANTES (10 μg/mice) subcutaneously on days -1, 0, 1, 2 and 3. Visualization of leukocyte recruitment using intravital microscopy was done at 1 and 3 days post-infection (dpi). The brain was removed for chemokine analysis by ELISA. Virus titration in cerebral tissue was done by TCID50.


Met-RANTES does not alter significantly virus titers at 1 dpi and 3 dpi after intracerebral injection of HSV-1. This treatment decreased leukocyte adhesion of microvasculature in C57BL/6 infected mice at 1 and 3 dpi. Treatment was also followed by a significant increase in chemokine levels, including CCL3, CCL5, CXCL1 and CXCL9, at 3 dpi.


CCL5/RANTES, a chemokine that binds to CCR1 and CCR5, seems to be relevant in the recruitment of leucocytes in an experimental model of severe HSV-1 encephalitis. However blocking of CCR1 and CCR5 does not affect HSV-1 replication, suggesting that other immune mechanisms are involved in this process.

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Correspondence to Márcia de Carvalho Vilela.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Vilela, M.d.C., Mansur, D., Lacerda-Queiroz, N. et al. Effect of CCR5 receptor antagonist (MET-RANTES) on leukocyte-endothelium interactions in an experimental model of herpetic encephalitis. BMC Proc 2 (Suppl 1), P10 (2008).

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