Therapeutic effect of a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito) on nitric oxide-mediated lung injury in a mouse infected with murine cytomegalovirus.
The therapeutic effect of a traditional Chinese medicine ren-shen-yang-rong-tang (Japanese name: Ninjin'yoeito, NYT) on murine cytomegalovirus (MCMV)-associated pneumonitis was examined. In MCMV-pneumonitis, IFN-gamma-induced nitric oxide (NO) mediates its pathogenesis. When mice, which had been infected with 0.2LD(50) of MCMV at 28 days previously, were intraperitoneally injected with anti-CD3 monoclonal antibody (mAb), MCMV-pneumonitis was induced in the lung, where high amounts of IFN-gamma-producing cells thereafter accumulated, accompanied by an elevation in the NO level in the serum and abundant expression of inducible NO synthase (iNOS) mRNA, thus resulting in all mice eventually dying. When the mice were orally treated with NYT (1000 mg/kg/day) once on the day of mAb injection and once the day after, the expression level of iNOS-mRNA was suppressed and NO level in the serum decreased. The survival rate improved from 0% to 57.1%. The pathological findings of the lungs in the NYT-treated mice were comparable to those of the uninfected controls. In contrast, NYT itself did not affect either the ratio of IFN-gamma-producing cells or MCMV titer. As a result, NYT had a therapeutic effect on MCMV-pneumonitis by decreasing the degree of inflammation mediated by the IFN-gamma-induced NO. It is also interesting to note that only two oral administrations of NYT had a therapeutic effect on viral disease.
Tanaka
Kazuo
K
Laboratory of Infectious Diseases, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan. claudio.kupfahl@imh.ma.uni-heidelberg.de
Sawamura
Sadaaki
S
D000818:Animals; D002452:Cell Count; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D011014:Pneumonia / Q000473:pathology / Q000821:virology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load
D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D007155:Immunologic Factors; C072867:ren-shen-yang-rong-tang; D009569:Nitric Oxide; D012313:RNA; D007371:Interferon-gamma; D004247:DNA; D052247:Nitric Oxide Synthase Type II