Effect of neutrophil depletion in acute cerebritis

Inhibition of the host's neutrophil response has been proposed as one means to reduce tissue damage in acute inflammation. If this approach can be applied in acute central nervous system (CNS) infection, the long-term morbidity, which occurs in CNS infection, might be reduced. Previous studies in models of CNS infection yielded conflicting results whether neutrophil depletion might be protective. To determine whether neutrophil depletion reduces tissue necrosis and cerebrovascular injury in experimental bacterial cerebritis, we depleted circulating neutrophils with an IgM monoclonal antibody, RP3, given after the start of the infection. RP3 treatment successfully depleted circulating neutrophils and reduced the extent of neutrophil influx into the cerebritis region. The extent of tissue necrosis, measured histologically, and the regional increase of blood-brain barrier (BBB) permeability were not inhibited by neutrophil depletion, and in animals treated with RP3 alone, the extent of tissue necrosis and BBB permeability tended to be larger than in S. aureus inoculated controls. We conclude that host neutrophils do not add to the tissue and cerebrovascular damage created by the intracerebral inoculation of a pathogenic bacteria, and the neutrophils serve to diminish local damage in the setting of a cerebritis.