Influence of rimonabant treatment on peripheral blood mononuclear cells; flow cytometry analysis and gene expression profiling.

The cannabinoid receptor type 1 (CB1) antagonist rimonabant has been used as treatment for obesity. In addition, anti-proliferative effects on mitogen-activated leukocytes have been demonstrated in vitro. We have previously shown that rimonabant (SR141716A) induces cell death in ex vivo isolated malignant lymphomas with high expression of CB1 receptors. Since CB1 targeting may be part of a future lymphoma therapy, it was of interest to investigate possible effects on peripheral blood mononuclear cells (PBMC) in patients treated with rimonabant. We therefore evaluated leukocyte subsets by 6 color flow cytometry in eight patients before and at treatment with rimonabant for 4 weeks. Whole-transcript gene expression profiling in PBMC before and at 4 weeks of rimonabant treatment was done using Affymetrix Human Gene 1.0 ST Arrays. Our data show no significant changes of monocytes, B cells, total T cells or T cell subsets in PBMC during treatment with rimonabant. There was a small but significant increase in CD3-, CD16+ and/or CD56+ cells after rimonabant therapy. Gene expression analysis detected significant changes in expression of genes associated with innate immunity, cell death and metabolism. The present study shows that normal monocytes and leukocyte subsets in blood remain rather constant during rimonabant treatment. This is in contrast to the induction of cell death previously observed in CB1 expressing lymphoma cells in response to treatment with rimonabant in vitro. These differential effects observed on normal and malignant lymphoid cells warrant investigation of CB1 targeting as a potential lymphoma treatment.