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

Almestrand S, Wang X, Jeppsson-Ahlberg Å, Nordgren M, Flygare J, Christensson B, Rössner S, Sander B - PeerJ (2015)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet and Karolinska University Hospital Huddinge , Stockholm , Sweden.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Percentage of peripheral blood mononuclear cells (PBMC) before and during treatment with rimonabant.PBMC were analyzed by flow cytometry before start of therapy and 4 weeks later and results are given as percentage of mononuclear cells in blood. Each data point represents results from one patient. In cases with no change in the frequency of a certain cell type the data point would fall on the line. The only statistically significant change was for CD3−, CD16+ and/or CD56+ cells (p = 0.049). For the other subsets the p-values were as follows: CD3+ p = 0.47; CD3 + CD4 + p = 0.25; CD3 + CD8 + p = 0.11; CD19+ p = 0.13; CD3–CD4+ p = 0.11. The mononuclear gate was defined by CD45 in combination with side and forward scatter. Within this gate the frequencies of CD3+ T cells, CD19+ B cells, CD3−, CD56+ and/or CD16+ cells (NK cells and subpopulation of CD16+ monocytes) and CD3−, CD4+ cells (monocytes and dendritic cells) were analyzed.
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fig-1: Percentage of peripheral blood mononuclear cells (PBMC) before and during treatment with rimonabant.PBMC were analyzed by flow cytometry before start of therapy and 4 weeks later and results are given as percentage of mononuclear cells in blood. Each data point represents results from one patient. In cases with no change in the frequency of a certain cell type the data point would fall on the line. The only statistically significant change was for CD3−, CD16+ and/or CD56+ cells (p = 0.049). For the other subsets the p-values were as follows: CD3+ p = 0.47; CD3 + CD4 + p = 0.25; CD3 + CD8 + p = 0.11; CD19+ p = 0.13; CD3–CD4+ p = 0.11. The mononuclear gate was defined by CD45 in combination with side and forward scatter. Within this gate the frequencies of CD3+ T cells, CD19+ B cells, CD3−, CD56+ and/or CD16+ cells (NK cells and subpopulation of CD16+ monocytes) and CD3−, CD4+ cells (monocytes and dendritic cells) were analyzed.

Mentions: Blood levels of mononuclear cells on eight obese patients were analyzed by flow cytometry before and during treatment with rimonabant. There were no significant changes in the relative frequencies of total CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells or CD3–CD4+ cells (monocytes and dendritic cells) in the patients during the treatment period (Table 1, graphically presented in Fig. 1) There was however a trend towards an increase in percentage of CD3−, CD16+/and or CD56+ cells (before treatment median 9% range 7–14%; after treatment median 12% range 9–15% p = 0.049) (Table 1 and Fig. 1).


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

Almestrand S, Wang X, Jeppsson-Ahlberg Å, Nordgren M, Flygare J, Christensson B, Rössner S, Sander B - PeerJ (2015)

Percentage of peripheral blood mononuclear cells (PBMC) before and during treatment with rimonabant.PBMC were analyzed by flow cytometry before start of therapy and 4 weeks later and results are given as percentage of mononuclear cells in blood. Each data point represents results from one patient. In cases with no change in the frequency of a certain cell type the data point would fall on the line. The only statistically significant change was for CD3−, CD16+ and/or CD56+ cells (p = 0.049). For the other subsets the p-values were as follows: CD3+ p = 0.47; CD3 + CD4 + p = 0.25; CD3 + CD8 + p = 0.11; CD19+ p = 0.13; CD3–CD4+ p = 0.11. The mononuclear gate was defined by CD45 in combination with side and forward scatter. Within this gate the frequencies of CD3+ T cells, CD19+ B cells, CD3−, CD56+ and/or CD16+ cells (NK cells and subpopulation of CD16+ monocytes) and CD3−, CD4+ cells (monocytes and dendritic cells) were analyzed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493638&req=5

fig-1: Percentage of peripheral blood mononuclear cells (PBMC) before and during treatment with rimonabant.PBMC were analyzed by flow cytometry before start of therapy and 4 weeks later and results are given as percentage of mononuclear cells in blood. Each data point represents results from one patient. In cases with no change in the frequency of a certain cell type the data point would fall on the line. The only statistically significant change was for CD3−, CD16+ and/or CD56+ cells (p = 0.049). For the other subsets the p-values were as follows: CD3+ p = 0.47; CD3 + CD4 + p = 0.25; CD3 + CD8 + p = 0.11; CD19+ p = 0.13; CD3–CD4+ p = 0.11. The mononuclear gate was defined by CD45 in combination with side and forward scatter. Within this gate the frequencies of CD3+ T cells, CD19+ B cells, CD3−, CD56+ and/or CD16+ cells (NK cells and subpopulation of CD16+ monocytes) and CD3−, CD4+ cells (monocytes and dendritic cells) were analyzed.
Mentions: Blood levels of mononuclear cells on eight obese patients were analyzed by flow cytometry before and during treatment with rimonabant. There were no significant changes in the relative frequencies of total CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells or CD3–CD4+ cells (monocytes and dendritic cells) in the patients during the treatment period (Table 1, graphically presented in Fig. 1) There was however a trend towards an increase in percentage of CD3−, CD16+/and or CD56+ cells (before treatment median 9% range 7–14%; after treatment median 12% range 9–15% p = 0.049) (Table 1 and Fig. 1).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet and Karolinska University Hospital Huddinge , Stockholm , Sweden.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus