Boost of mucosal secretory immunoglobulin A response by clarithromycin in paediatric influenza.
http://www3.interscience.wiley.com/journal/122660780/abstract?CRETRY=1&SRETRY=0
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Sawabuchi T, Suzuki S, Iwase K, Ito C, Mizuno D, Togari H, Watanabe I, Talukder SR, Chida J, Kido H.
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima 770-8503, Japan.
BACKGROUND AND OBJECTIVE: The antiviral neuraminidase inhibitor oseltamivir (OSV) is used to treat influenza. The macrolide clarithromycin (CAM) is used to treat bacterial infections and has anti-inflammatory and immunomodulatory activities. This retrospective study investigated the immunomodulatory effects of CAM in children presenting with influenza A. METHODS: The study recruited 40 children with acute influenza, and grouped them according to the treatment received: 5-day treatment with OSV (n = 14), CAM (n = 8), OSV + CAM (n = 12) and untreated (n = 6). The before and after treatment comparisons were made of the level of secretory IgA (sIgA) against influenza A virus (H3N2) and (H1N1), total sIgA, viral RNA copy numbers in nasopharyngeal aspirates and disease symptoms. RESULTS: Infection induced anti-viral mucosal sIgA in the nasopharyngeal aspirates of most patients of all treatment groups. Particularly prominent increases in the levels were found in the CAM and OSV + CAM groups. Low induction of anti-viral sIgA was observed in the OSV group, but the addition of CAM to OSV augmented sIgA production and restored local mucosal sIgA levels. The frequency of residual cough in the OSV + CAM group was significantly lower than in the other groups including the group treated with OSV. CONCLUSIONS: CAM boosted the nasopharyngeal mucosal immune response in children presenting with influenza A, even in those treated with OSV who had low production of mucosal anti-viral sIgA, and alleviated the symptoms of influenza.
Clarithromycin inhibits type A seasonal influenza virus infection in human airway epithelial cells.
free full text here : http://jpet.aspetjournals.org/content/early/2009/12/29/jpet.109.162149.long
Yamaya M, Shinya K, Hatachi Y, Kubo H, Asada M, Yasuda H, Nishimura H, Nagatomi R.
1 Tohoku University School of Medicine;
Human influenza viruses attach to sialic acid with an alpha2,6linkage (SAalpha2,6Gal) on the airway epithelial cells, and the entry of the viruses into the cells and uncoating of the viruses require low pH of endosomes. Bafilomycin A(1), a macrolide antibiotic and the specific vascular-ATPase inhibits growth of type A and type B human influenza viruses in Madin Darby Canine Kidney cells.
However, the inhibitory effects of clinically used macrolide antibiotics on influenza virus infection in human airways have not been studied. To examine the effects of clarithromycin on seasonal human influenza virus infection, cultured human tracheal epithelial cells were infected with type A influenza virus (H(3)N(2)). Influenza virus infection increased viral titers and the content of cytokines, including interleukin (IL)-1beta and IL-6, in supernatant fluids, and viral RNA in the cells. Clarithromycin reduced viral titers and the content of cytokines in supernatant fluids, viral RNA in the cells, and the susceptibility to virus infection. Clarithromycin reduced the expression of SAalpha2,6Gal, a receptor for human influenza virus, on the mucosal surface of human tracheae, and the number and fluorescence intensity of acidic endosomes in the cells from which viral ribonucleoproteins enter into the cytoplasm. Furthermore, clarithromycin reduced nuclear factor-kappaB (NF-kappaB) proteins including p50 and p65 in the nuclear extracts. These results suggest that clarithromycin may inhibit seasonal human influenza virus infection by reducing SAalpha2,6Gal partly through the inhibition of NF-kappaB, and by increasing pH in endosomes in airway epithelial cells. Clarithromycin may modulate airway inflammation in influenza virus infection.
PMID: 20040578 [PubMed - as supplied by publisher]