Adjuvant protection against bacterial infection in granulocytopenic mice

The hypothesis that the induction of nonspecific resistance to infection by immunostimulation prior to drug-induced granulocytopenia would afford increased protection to subsequent bacterial challenge was tested in a murine model of infection with Pseudomonas aeruginosa or Staphylococcus aureus in mice rendered granulocytopenic with cyclophosphamide. Prior intraperitoneal immunostimulation of mice with complete Freund's adjuvant (CFA) or Mycobacterium bovis (Bacille Calmette-Guèrin; BCG) increased the 50% lethal dose in mice challenged subcutaneously with P. aeruginosa, but only CFA protected against challenge with S. aureus. The degree of protection was 1-2 log 10. Corynebacterium parvum provided no protection against infection with P. aeruginosa. The protective effect observed with CFA and BCG substantiates our hypothesis and indicates that nonspecific immunostimulation may be of value in protection of granulocytopenic patients from opportunistic infections.