Pathophysiology of Candida albicans meningitis in normal, neutropenic, and granulocyte transfused dogs.

Candida albicans meningitis was induced in normal dogs and in dogs rendered neutropenic (<500/cu mm) in order to follow cerebrospinal fluid (CSF) granulocyte migration patterns, quantitative fungal cultures. and clinical events. Dogs received an intrathecal challenge with i07 C. albicans, and CSF samples were monitored. Neutropenia was produced by administration of cyclophosphamide 5 days before fungal challenge. Granulocytes for transfusion were obtained from normal donors by semicontinuous centrifugation. In normal dogs, CSF neutrophilic pleocytosis began 3 hr after fungal challenge and reached a maximum within 24 hr. These dogs cleared their infection and remained clinically well. Nontransfused neutropenic dogs failed to show granulocyte responses in CSF and died within 84 hr of meningitis. In a controlled study of 8 pairs of neutropenic dogs, one partner received a single granulocyte transfusion 24 hr following fungal challenge. Transfusions were followed by significant increments (p < 0.025) in CSF pleocytosis compared to controls that correlated with concurrent peripheral blood increments (r = 0.8). Six of eight transfused dogs survived longer than their nontransfused partners. Four dogs that had received prior immunization with donor tissue failed to show CSF granulocyte increments following transfusion. It was concluded that: (A) the model provides for assay of in vivo kinetics of transfused granulocytes during a local infection, (B) in normal dogs the initial CSF granulocyte response is associated with resolution of the infection; (C) transfused granulocytes migrate into the CSF in proportion to peripheral blood increments; and (D) infusion of granulocytes into sensitized recipients demonstrates no biologic effect.