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Statins improve innate resistance to pneumococcal pneumonia via lung macrophage NOS3
Author(s) -
Yang Zhiping,
Ghosh Sanjukta,
Kobzik Lester
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.111.5
Subject(s) - pneumococcal pneumonia , pravastatin , pneumonia , medicine , streptococcus pneumoniae , innate immune system , immunology , bacterial pneumonia , neutrophilia , lung , macrophage , phagocytosis , statin , lipopolysaccharide , immune system , microbiology and biotechnology , biology , cholesterol , antibiotics , in vitro , biochemistry
Statins have been linked epidemiologically to better outcomes in pneumonia, but the mechanisms are unclear. We investigated the role of statins in boosting innate immune resistance to bacterial pneumonia using a mouse model. In bacterial pneumonia induced by Strep. pneumoniae (serotype 3, 100K CFU i.n.), pravastatin (50 mg/kg i.p.) caused improved bacterial clearance (% bacterial left alive in lungs at 24 hours, mean ± SD: control, 65 ± 22 vs statin‐treated, 17 ± 11; n = 7 female mice/grp), reduced BAL neutrophilia and improved survival. The mechanisms were linked to activation of lung macrophage NOS3, based on statin‐induced activation of macrophage NOS3 (increased phosphorylation of serine 1177 on Western blot analysis), statin‐mediated enhancement of macrophage killing of pneumococci in vitro and absence of a beneficial effect of statins in NOS3‐deficient mice. In addition, statin treatment of mice with secondary bacterial pneumonia after influenza resulted in prolonged survival. The data support the potential benefit of short‐term therapy with statins to boost innate resistance to pneumococcal pneumonia. Supported by NIH HL083436, ES11008, ES00002.