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In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of severe pneumococcal pneumonia

التفاصيل البيبلوغرافية
العنوان: In vivo efficacy of KRP-109, a novel elastase inhibitor, in a murine model of severe pneumococcal pneumonia
المؤلفون: Yoshihiro Yamamoto, Nobuko Araki, Shimeru Kamihira, Yoshitomo Morinaga, Koichi Yamada, Hiroshi Kakeya, Katsunori Yanagihara, Hiroo Hasegawa, Koichi Izumikawa, Shigeru Kohno, Yosuke Harada
المصدر: Pulmonary Pharmacology & Therapeutics. 24:660-665
بيانات النشر: Elsevier BV, 2011.
سنة النشر: 2011
مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Streptococcus pneumonia, Pyrrolidines, Serine Proteinase Inhibitors, Lung injury, medicine.disease_cause, Mice, Neutrophil elastase, Streptococcus pneumoniae, medicine, Animals, Pharmacology (medical), Lung, medicine.diagnostic_test, biology, business.industry, Biochemistry (medical), Pneumonia, Pneumococcal, medicine.disease, Immunomodulation therapy, Benzoxazines, respiratory tract diseases, Disease Models, Animal, Pneumonia, Elastase inhibitor, Bronchoalveolar lavage, medicine.anatomical_structure, Pneumococcal pneumonia, Immunology, Mice, Inbred CBA, biology.protein, Female, Leukocyte Elastase, business, Bronchoalveolar Lavage Fluid
الوصف: KRP-109 is a novel specific inhibitor of neutrophil elastase (NE). Various studies suggest that NE inhibitors reduce lung injury associated with systemic inflammatory response syndrome (SIRS). In this study, the efficacy of KRP-109 was examined using a murine model of severe pneumonia induced by Streptococcus pneumoniae (S.pneumoniae). Female mice (CBA/J, aged 5 weeks) were inoculated intranasally with penicillin-susceptible S.pneumoniae (ATCC49619 strain, 2.5×10(8)CFU/mouse). KRP-109 (30 or 50mg/kg) or physiological saline as a control was administered intraperitoneally every 8h beginning at 8h after inoculation, and survival rate was evaluated over 7 days. Histopathological and bacteriological analyses of the lung, and bronchoalveolar lavage were performed at 48h post-infection. The mice treated with KRP-109 (KRP-109 mice) tended to have higher survival rate than those given saline. The lung tissues of the KRP-109 mice had few neutrophils in the alveolar walls and less inflammation. Furthermore, KRP-109 decreased significantly total cell and neutrophil counts, and cytokine levels (interleukin 1β and macrophage inflammatory protein 2) in bronchoalveolar lavage fluid. Viable bacterial numbers in lung were not influenced by treatment of KRP-109. The present results indicate that KRP-109 reduces lung inflammation in a murine model, and that KRP-109 may be useful for the treatment of patients with severe pneumonia.
Pulmonary Pharmacology & Therapeutics, 24(6), pp.660-665; 2011
وصف الملف: application/pdf
تدمد: 1094-5539
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9231f2cf57f67a3e6391b749f7dc9188
https://doi.org/10.1016/j.pupt.2011.08.001
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....9231f2cf57f67a3e6391b749f7dc9188
قاعدة البيانات: OpenAIRE
الوصف
تدمد:10945539