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Fluvastatin enhances IL-33-mediated mast cell IL-6 and TNF production. | LitMetric

AI Article Synopsis

  • Statins, like fluvastatin, are known for lowering cholesterol but also affect inflammation by inhibiting small G protein functions.
  • Fluvastatin enhances IL-33-induced production of TNF and IL-6 in mast cells, which requires stem cell factor and may involve reduced production of isoprenoids.
  • Some statins have shown unexpected pro-inflammatory effects, highlighting the need to understand their diverse impacts, especially as potential treatments for inflammatory disorders.

Article Abstract

Statins are HMG-CoA reductase inhibitors prescribed for lowering cholesterol. They can also inhibit inflammatory responses by suppressing isoprenylation of small G proteins. Consistent with this, we previously found that fluvastatin suppresses IgE-mediated mast cell function. However, some studies have found that statins induced pro-inflammatory cytokines in macrophages and NK cells. In contrast to IgE signaling, we show that fluvastatin augments IL-33-induced TNF and IL-6 production by mast cells. This effect required the key mast cell growth factor, stem cell factor (SCF). Treatment of IL-33-activated mast cells with mevalonic acid or isoprenoids reduced fluvastatin effects, suggesting fluvastatin acts at least partly by reducing isoprenoid production. Fluvastatin also enhanced IL-33-induced NF-κB transcriptional activity and promoted neutrophilic peritonitis in vivo, a response requiring mast cell activation. Other statins tested did not enhance IL-33 responsiveness. Therefore, this work supports observations of unexpected pro-inflammatory effects of some statins and suggests mechanisms by which this may occur. Because statins are candidates for repurposing in inflammatory disorders, our work emphasizes the importance of understanding the pleiotropic and possible unexpected effects of these drugs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782378PMC
http://dx.doi.org/10.1016/j.cellimm.2021.104457DOI Listing

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