Statins repress needle-like carbon nanotube- or cholesterol crystal-stimulated IL-1β production by inhibiting the uptake of crystals by macrophages

The Immunomodulatory Effects of Statins on Macrophages

“…Biological (cell type, seeding density, and medium composition) and technical (edge effect, drug type and dose, incubation conditions, treatment time, and duration time) parameters can introduce variation, and this may contribute to the differential effects observed between the various investigations of statins' effects on macrophage inflammatory responses. Indeed, a recent study that reviewed the effects of pravastatin treatment on various macrophage cell types noted that it acted in synergy with LPS to promote IL-1β expression in BMDMs but markedly repressed its production in both peripheral-blood monocyte and THP1-derived macrophages [94]. Taking this into consideration, it is interesting to note that many of the studies involving the investigation of BMDMs support the idea of statins enhancing a pro-inflammatory macrophage response to some degree and, more specifically, found statins to enhance IL-1b transcription (Table 2).…”

“…[93] THP1 derived macrophages Impaired MWCNT-elicited IL-1β secretion. [94] Human PBMC derived macrophages Decreased the activity of iNOS in M1 macrophages. [103] Table 2.…”

“…Lindholm and Nilsson reported that in combination with aggregated LDL (agLDL) loading, statin treatment enhanced secretion of IL-1β and IL-8 but had no effect on TNFα or IL-6 secretion in human primary monocyte-derived macrophages isolated from buffy coats [120]. Cui et al also reported statin treatment to strongly enhance mature IL-1β release in murine BMDMs stimulated with a combination of LPS and cholesterol crystals but noted the opposite to be true in THP-1 derived macrophages [94]. Interestingly, despite the conflicting data between macrophage cell types, these effects were all reported to be isoprenoid dependent [94,120].…”

“…Cui et al also reported statin treatment to strongly enhance mature IL-1β release in murine BMDMs stimulated with a combination of LPS and cholesterol crystals but noted the opposite to be true in THP-1 derived macrophages [94]. Interestingly, despite the conflicting data between macrophage cell types, these effects were all reported to be isoprenoid dependent [94,120]. At present, it remains unclear which TLR-pathway signalling elements are affected by statin treatment in ox-and agLDL-stimulated macrophages but, given that (for reasons not completely understood) different TLR4 stimuli induce different cellular responses [157,158], future studies may find the involvement of signalling components outside of those noted in the LPS experiments.…”

Functional Phenotypes of Intraplaque Macrophages and Their Distinct Roles in Atherosclerosis Development and Atheroinflammation

“…Another in vitro study demonstrated that different statins (pitavastatin, atorvastatin, fluvastatin, and lovastatin) could inhibit the uptake of carbon nanoparticles and cholesterol crystals by macrophages. This led to reduced production of IL-1β therefore providing for another possible anti-inflammatory effect of statins [ 77 ]. These results indicate that the pleiotropic actions of statins are worthy to be studied further and may manifest especially at a cellular level, specifically affecting plaque macrophages.…”