Effect of liposome-encapsulation on immunomodulating and antiviral activities of interferon-gamma 1.
The effect of liposome-encapsulation on the immunomodulating and antiviral activities of interferon-gamma (IFN-gamma) was evaluated in this study. The immunomodulating activity was measured by increases in phagocytic activity and in nitric oxide production by peritoneal macrophages from mice treated with both free and LIP-IFN-gamma (4000 U/mouse, intraperitoneal injection). Resident peritoneal macrophages harvested from mice treated with free unencapsulated IFN-gamma or muramyl dipeptide showed significant increases in macrophage yield, and enhanced ability to phagocytize zymosan particles. In mice treated with liposome-encapsulated IFN-gamma (LIP-IFN-gamma), both macrophage yield and phagocytic activity further increased by 2-fold over unencapsulated IFN-Y. In addition, the activation of peritoneal macrophages with LIP-IFN-gamma showed enhanced production of NO when the cells were cultured ex vivo. Using a murine respiratory influenza infection model, intranasally administered LIP-IFN-gamma conferred protection to 70% in mice challenged intranasally with 10 LD50 doses of influenza A/PR/8 virus compared with a 20% survival rate using free IFN-gamma. Together these results suggest that liposome-encapsulation increases the immunomodulating and antiviral activities of IFN-gamma. Liposome-encapsulation of IFN-gamma may provide additional therapeutic advantages by reducing IFN-gamma toxicity while prolonging its body retention.
Saravolac
E G
EG
Medical Countermeasures Section, Defence Research Establishment Suffield, Ralston, Canada.
Kournikakis
B
B
Gorton
L
L
Wong
J P
JP
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000517:prevention & control*; D007371:Interferon-gamma / Q000494:pharmacology*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects
D000998:Antiviral Agents; D008081:Liposomes; D009573:Nitrites; D007371:Interferon-gamma