[show abstract][hide abstract] ABSTRACT: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection.
We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice) to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection.
Using the established, very susceptible 2009 Pandemic Influenza A (H1N1) mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1pandemics.
PLoS ONE 01/2012; 7(8):e44110. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: The use of corticosteroids in the management of pneumonia is still a controversial issue. The physicians in daily clinical practice often use corticosteroids in patients with pneumonia for different reasons all over the world. As an example of real life is the frequent use of corticosteroids to treat patients with pneumonia due to H1N1 pandemic influenza in spite of WHO' statements that clearly discouraged this therapy. In fact, the literature up to august 2012 reported a total of 6,650 patients with pneumonia due to H1N1 virus infection (of whom 2,515 were ICU patients): corticosteroids were used with various dose regimen in 2404 patients (37.8%). The attitude of international guidelines on pneumonia in using steroids do not help the clinician to clearly choice when and how to treat pneumonia with steroids. However, stress doses of corticosteroids are suggested by some major guidelines on community-acquired pneumonia in case of severe episodes with sepsis. To date, there are 10 randomised controlled trials assessing the effectiveness of corticosteroids for community-acquired pneumonia globally involving 1090 participants. Most of the trials adopted stress doses of glucorticoids for 4-7 days. The evidence from these trials taken separately is weak due to limitations of the studies themselves, but a Cochrane review and a systematic review found benefit using prolonged low doses of glucocorticoids in severe community-acquired pneumonia. Moreover, such a strategy decreases vasopressor dependency and appears to be safe. Nevertheless, larger trials with more patients and clinically important end-points were claimed to provide robust evidence. Finally, infection surveillance is critical in patients treated with corticosteroids, and to prevent the rebound phenomenon, the drug should be weaned slowly.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 06/2012; 77(2):94-101.
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