Mechanisms of Rapid Nonspecific Resistance Induced by Immunomodulators: Delineation Using Selective Depletion of Cells
Abstract
Pyrimidinone, muramyl dipeptide and tripeptide, detoxified lipopolysaccharide and trehalose dimycolate immunomodulators have been evaluated for ability to increase nonspecific resistance of CD-1 mice of Listeria monocytogenes, encephalomyocarditis virus and herpes simplex virus type 2. The brominated pyrimidinone was very effective in prophylactic treatment against the viral infections, but not against listeria infection by the regimens tested. Of the bacterial cell wall type immunomodulators, detoxified endotoxin and trehalose dimycolate appeared to be the most effective. Additional experiments to directly evaluate the same doses, regimens and vehicles are planned in normal CD-1 mice. The most effective agents will be tested for ability to enhance resistance in the face of 89Sr-induced monocytopenia, granulocytopenia and depressed NK cell activity. The mechanism of activation, and effects of the C. parvum immunomodulator have been investigated in 89Sr treated or congenitally defective Sl/Sld mice; both provide models for deficient bone marrow dependent functions. Our studies in the 89Sr system have established that C. parvum activation of peritoneal macrophages (M0) is associated with a marked acute and persistent PMN inflammatory response. In the CD-1 mouse, we have extended our observations with C. parvum to several other biologic response modifiers known to activate M0 for antitumor activity (pyran copolymer and M. bovis strain BCG). We have also begun developing liposome methodology for depletion of tissue M0.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 30, 1985
- Accession Number
- ADA157543
Entities
People
- A. Volkman
- P. S. Morahan