Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice.
Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is used for treating chronic lower respiratory tract infections. It has been shown that free radicals, such as the superoxide anion and nitric oxide (NO), are pathogenic molecules in viral disease. Much attention has been given to a critical role of NO in the pathologic events of various inflammatory diseases. In the present study, we evaluated the effects of EM on influenza-virus-induced pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67 (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally, from Days 1 to 6 after infection), significantly improved the survival rate of mice infected with influenza virus, and the survival rate of the virus-infected mice at Day 20 after infection increased in a dose-dependent fashion with EM administered to the animals, from 14% among controls to 42% among animals given EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on Day 6 after infection. Simultaneously, the number of inflammatory cells recovered in lung lavage fluid 6 d after virus infection was significantly reduced by the treatment with EM. The EM treatment resulted in a dose-dependent decrease in the level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase (NOS)-inducting potential in the lungs of the virus-infected mice. These results indicate that EM may have substantial therapeutic value for various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing NO overproduction in the lung.
Sato
K
K
First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Suga
M
M
Akaike
T
T
Fujii
S
S
Muranaka
H
H
Doi
T
T
Maeda
H
H
Ando
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002423:Cause of Death; D004305:Dose-Response Relationship, Drug; D004917:Erythromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D005609:Free Radicals / Q000009:adverse effects; D009980:Influenza A virus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000009:adverse effects / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000187:drug effects; D009573:Nitrites / Q000097:blood; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013481:Superoxides / Q000009:adverse effects; D015996:Survival Rate
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D005609:Free Radicals; D009566:Nitrates; D009573:Nitrites; D013481:Superoxides; D009569:Nitric Oxide; D004917:Erythromycin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase