Free and liposome-encapsulated immunomodulators stimulating the nonspecific resitance against bacterial infections

In this thesis MTPPE and IFN--y in the free form or in the liposome-encapsulated form were studied for their efficacy to enhance the nonspecific resistance to bacterial infections. The aim was to obtain an insight in the possibilities and restrictions of treatment with these immunomodulators. This was investigated in experimental bacterial infections in mice. In one experimental model, infections were induced with Listeria monocytogenes after intravenous inoculation. This bacterium is easily taken up by cells of the MPS and is able to resist killing by these cells. It is investigated whether the cells of the MPS, when stimulated by MTPPE or IFN--y are able to kill L. monocytogenes. In other experimental models infections were induced with Klebsiella pneumoniae, a bacterium that, when it is not opsonized by specific antibodies, is poorly taken up by cells of the MPS. It is investigated whether in the non-immune host the cells of the MPS, when stimulated by MTPPE are able to effectively phagocytose K. pneumonioe. When K. pneumoniae infection was induced by intravenous inoculation, about 80% of the bacteria were cleared from the blood by liver and spleen, resulting in death of all mice due to septicemia ('artificially-induced septicemia'). In a more clinically relevant model of infection K. pneumoniae was inoculated intraperitoneally. In this model multiplication of bacteria in the peritoneal cavity resulted in appearance of bacteria in the blood at regular intervals. Eventually all mice died due to septicemia ('naturally- induced septicemia').