期刊
COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES
卷 56, 期 -, 页码 6-13出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.cimid.2017.11.002
关键词
Matrix metalloproteinase-9; Macrolide; Clarithromycin; Evans' blue extravasation; Influenza A virus infection; Multiple organ failure
资金
- Grants-in-Aid for Scientific Research [17K16267, 16H05348] Funding Source: KAKEN
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-gamma. 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.
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