Viral pre-challenge increases central nervous system inflammation after intracranial interleukin-1β injection.

INTRODUCTION: Systemic inflammation has been shown to significantly worsen the outcome of neurological disease. However, after acute injuries to the brain both pre- and post-conditioning with bacterial endotoxin has been shown to reduce leukocyte recruitment to the CNS. Here, we sought to determine whether viral pre-challenge would have an effect on the outcome of acute CNS inflammation that was distinct from endotoxin. METHODS: Animals received a single intracranial microinjection of IL-1β in the presence or absence of a viral pre-challenge 24 hours prior to surgery. Liver and brain tissue were analysed for chemokine expression by qRT-PCR and leukocyte and monocyte infiltration 12 hours, 3 days and 7 days after the IL-1β injection. RESULTS: Here, a single injection of adenovirus prior to IL-1β injection resulted in adhesion molecule expression, chemokine expression and the recruitment of neutrophils to the injured CNS in significantly higher numbers than in IL-1β injected animals. The distribution and persistence of leukocytes within the CNS was also greater after pre-challenge, with neutrophils being found in both the ipsilateral and contralateral hemispheres. Thus, despite the absence of virus within the CNS, the presence of virus within the periphery was sufficient to exacerbate CNS disease. CONCLUSIONS: These data suggest that the effect of a peripheral inflammatory challenge on the outcome of CNS injury or disease is not generic and will be highly dependent on the nature of the pathogen.