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 lo ng-term morbidity, which occurs in CNS infection, might be reduced. Pr evious 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 inju ry in experimental bacterial cerebritis, we depleted circulating neutr ophils with an IgM monoclonal antibody, RP3, given after the start of the infection. RP3 treatment successfully depleted circulating neutrop hils and reduced the extent of neutrophil influx into the cerebritis r egion. 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 alo ne, the extent of tissue necrosis and BBB permeability tended to be la rger than in S. aureus inoculated controls. We conclude that host neut rophils do not add to the tissue and cerebrovascular damage created by the intracerebral inoculation of a pathogenic bacteria, and the neutr ophils serve to diminish local damage in the setting of a cerebritis. (C) 1998 Elsevier Science B.V. All rights reserved.