Antiherpes activity of chemically synthesized lipid A-subunit analogue GLA-60 in immunosuppressed mice |
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Authors: | S Ikeda T Tominaga C Nishimura J Y Homma M Kiso A Hasegawa |
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Institution: | School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. |
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Abstract: | 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. |
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