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Clarithromycin suppresses induction of monocyte chemoattractant protein-1 and matrix metalloproteinase-9 and improves pathological changes in the lung

tetano

Editor, Senior Moderator
Comp Immunol Microbiol Infect Dis. 2018 Feb;56:6-13. doi: 10.1016/j.cimid.2017.11.002. Epub 2017 Nov 23.
[h=1]Clarithromycin suppresses induction of monocyte chemoattractant protein-1 and matrix metalloproteinase-9 and improves pathological changes in the lungs and heart of mice infected with influenza A virus.[/h] Takahashi E[SUP]1[/SUP], Indalao IL[SUP]1[/SUP], Sawabuchi T[SUP]1[/SUP], Mizuno K[SUP]1[/SUP], Sakai S[SUP]1[/SUP], Kimoto T[SUP]1[/SUP], Kim H[SUP]1[/SUP], Kido H[SUP]2[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] The influenza A virus (IAV)-cytokine-trypsin/matrix metalloproteinase-9 (MMP-9) cycle is one of the important mechanisms of multiple organ failure in severe influenza. Clarithromycin, a macrolide antibiotic, has immune modulatory and anti-inflammatory effects. We analyzed the effects of clarithromycin on the induction of chemokines, cytokines, MMP-9, trypsin, vascular hyper-permeability and inflammatory aggravation in mice with IAV infection. IAV/Puerto Rico/8/34(H1N1) infection increased the levels of monocyte chemoattractant protein-1 (MCP-1) and cytokines in serum, and MMP-9 and trypsin in serum and/or the lungs and heart. Clarithromycin significantly suppressed the induction of serum MCP-1 and MMP-9 and vascular hyperpermeability in these organs in the early phase of infection, but did not suppress the induction of trypsin, IL-6 or IFN-γ. Histopathological examination showed that clarithromycin tended to reduce inflammatory cell accumulation in the lungs and heart. These results suggest that clarithromycin suppresses infection-related inflammation and reduces vascular hyperpermeability by suppressing the induction of MCP-1 and MMP-9.


[h=4]KEYWORDS:[/h] BBB; Clarithromycin; Evans? blue extravasation; IAV; Influenza A virus infection; MC; MOF; Macrolide; Matrix metalloproteinase-9; Multiple organ failure; PID; PR8; blood-brain barrier; influenza A virus; influenza A/Puerto Rico/8/34(H1N1); methyl cellulose; multiple organ failure; pfu; plaque-forming units; post-infection day

PMID: 29406285 DOI: 10.1016/j.cimid.2017.11.002
 
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