Protection against murine cytomegalovirus infection in aged mice and mice with severe combined immunodeficiency disease with the biological response modifiers polyribosinic-polycytidylic acid stabilized with L-lysine and carboxymethylcellulose, maleic anhydride divinyl ether and colony stimulating factor 1.
A variety of biological response modifiers (BRMs) have provided antiviral protection to immunocompetent mice, and this prompted us to determine their efficacy against murine cytomegalovirus (MCMV) infection in immunocompromised mice-including the profoundly immunocompromised SCID mice and C57Bl/6 and B6D2F1 aged mice. SCID mice showed a marked decrease (> 20-fold) in resistance to MCMV, while there was a slight decrease (3-fold) in aged mice. In BRM antiviral protection studies, SCID mice were almost completely protected against MCMV infection by the pleiotropic immunomodulators, MVE-2 and pICLC, but much less by the more selective CSF-1. pICLC-induced IFN and NK cell cytotoxicity were maintained in SCID mice, suggesting that pleiotropic immunomodulatory effects may be required for antiviral protection in such a profoundly immunocompromised model. pICLC also effectively protected aged mice against lethal MCMV infection and effectively induced IFN. These results emphasize the potential for BRM treatment in immunocompromised hosts.
Kunder
S C
SC
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Wu
L
L
Morahan
P S
PS
D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology / Q000517:prevention & control*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000627:therapeutic use*; D007372:Interferons / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011070:Poly I-C / Q000627:therapeutic use*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011713:Pyran Copolymer / Q000627:therapeutic use*; D016511:Severe Combined Immunodeficiency / Q000150:complications*
D007155:Immunologic Factors; D011107:Polylysine; D011713:Pyran Copolymer; C019531:poly ICLC; D016173:Macrophage Colony-Stimulating Factor; D007372:Interferons; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C