Antiherpes activity of chemically synthesized lipid A-subunit analogue GLA-60 in immunosuppressed mice.
Intraperitoneal administration of 10 micrograms GLA-60, a chemically synthesized lipid A analogue, to mice one day after treatment with 200 mg/kg of cyclophosphamide (CY) significantly increased the number of macrophages, lymphocytes and polymorphonuclear leukocytes (PMNs) in the peritoneal cavity. The intrinsic antiviral activity of macrophages against herpes simplex virus type 1 (HSV-1) as well as natural killer (NK) activity against YAC-1 target cells was stimulated by administration of GLA-60 to CY-immunosuppressed mice. When the mice were administered GLA-60 prior to HSV-1 infection, virus growth was inhibited and the mortality rate of infected mice was reduced. Thus, GLA-60 is a potent immunomodulator achieving its antiviral action through enhancement of nonspecific host defense mechanisms. Combined treatment of GLA-60 with the antiviral agent acyclovir (ACV) resulted in greater protection against HSV-1 in the CY-immunosuppressed mice than did single treatment with either GLA-60 or ACV.
Ikeda
S
S
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Tominaga
T
T
Nishimura
C
C
Homma
J Y
JY
Kiso
M
M
Hasegawa
A
A
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development*
D000998:Antiviral Agents; D008050:Lipid A; C056260:GLA 60; D003520:Cyclophosphamide