Impact of anti-inflammatory molecule Statin (Atorvastatin) treatment of the graft in the context of mobilized stem cell transplantation
Statins are mostly known for inhibiting mevalonate and cholesterol biosynthesis, however a new biological function in hampering immune response against autoantigens and alloantigens has been identified. Statins drive Th2 polarization, enrich the Tregs subset and limits lymphocyte trafficking to sites of inflammation, suggesting its role in promoting an overall anti-inflammatory environment. Parallelly Mielcarek’s group showed that donor statin usage was associated with protection against severe acute graft-versus-host disease (GVHD) after hematopoietic cell transplant (HCT) from HLA-identical related donors.
We hypothesize that statin treatment can decrease the inflammatory activation status of graft cells, therefore reducing the risk of developing GVHD after HCT. To test it, HLA-identical related donors were treated with atorvastatin (statin) for 10 days prior the collection of peripheral blood stem cells.
We received cells from 38 subjects at baseline, 10 days after statin and pre-infusion time-points, from Dr. Hans Peter Kiem and Marco Mielcarek. These samples were tested for innate and adaptive immune responses using flow cytometry. Additionally, plasma were also collected and analyzed for its composition of 23 anti and pro-inflammatory cytokines. Initial analysis has shown that statin alone is capable of modulating the proportion of immune subsets. Multivariate analysis is being currently performed in order to build a model that explains the global effects of statin in innate and adaptive immune cells.