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Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy.

Khanna A, Plummer M, Bromberek K, Woodliff J, Hariharan S - Med Immunol (2002)

Bottom Line: Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute).RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone.Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine (Nephrology), Medical College of Wisconsin, Milwaukee WI-53226, USA. akkhanna@mcw.edu

ABSTRACT
BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL. Blood was drawn on day zero and 14 days post treatment. Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute). The mRNA expression was studied by RT-PCR and serum levels of cytokines were quantified by ELISA and a cytokine bead array system. RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone. The mRNA expression of proinflammatory cytokines TNF-alpha (p < 0.05), cyclins G (p < 0.01) and E (p < 05) were decreased, and of TGF-beta (p < 0.03) and p21 (p < 0.05) were increased in patients treated with this combination. Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination. CONCLUSION: These novel findings demonstrate that addition of SRL to TAC therapy enhances immuno modulation and causes increased immunosuppression providing a rationale for this concomitant therapy.

No MeSH data available.


Related in: MedlinePlus

Effect of different treatment protocols on lymphocyte proliferation: Peripheral blood mononuclear cells from the blood of renal transplants obtained on (day # 0) and on (day # 14) were separated by ficoll-hypaque. [3H]-thymidine uptake was quantified as counts per minute (CPM) using a liquid scintillation counter. The open bars represent the proliferation data (Mean ± SEM) of lymphocyte proliferation from patients treated with TAC/MMF/AZA and steroids and closed bars represent data after addition of SRL to TAC (day # 14) without MMF/AZA.
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Figure 2: Effect of different treatment protocols on lymphocyte proliferation: Peripheral blood mononuclear cells from the blood of renal transplants obtained on (day # 0) and on (day # 14) were separated by ficoll-hypaque. [3H]-thymidine uptake was quantified as counts per minute (CPM) using a liquid scintillation counter. The open bars represent the proliferation data (Mean ± SEM) of lymphocyte proliferation from patients treated with TAC/MMF/AZA and steroids and closed bars represent data after addition of SRL to TAC (day # 14) without MMF/AZA.

Mentions: The proliferation of lymphocytes from patients treated with TAC and SRL were compared with lymphocytes from patients treated with TAC and MMF/Aza. The results are shown in Figure 2 which, demonstrated a significant inhibition of proliferation of lymphocytes from patients with TAC and SRL compared to TAC plus MMF/Aza. (PHA: 17510 ± 4094 vs 10963 ± 3008 p < 0.05; ConA: 23995 ± 2449 vs 12124 ± 2946 p < 0.006; and anti-CD3: 27089 ± 1557 vs 16093 ± 3097 p < 0.005).


Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy.

Khanna A, Plummer M, Bromberek K, Woodliff J, Hariharan S - Med Immunol (2002)

Effect of different treatment protocols on lymphocyte proliferation: Peripheral blood mononuclear cells from the blood of renal transplants obtained on (day # 0) and on (day # 14) were separated by ficoll-hypaque. [3H]-thymidine uptake was quantified as counts per minute (CPM) using a liquid scintillation counter. The open bars represent the proliferation data (Mean ± SEM) of lymphocyte proliferation from patients treated with TAC/MMF/AZA and steroids and closed bars represent data after addition of SRL to TAC (day # 14) without MMF/AZA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC149406&req=5

Figure 2: Effect of different treatment protocols on lymphocyte proliferation: Peripheral blood mononuclear cells from the blood of renal transplants obtained on (day # 0) and on (day # 14) were separated by ficoll-hypaque. [3H]-thymidine uptake was quantified as counts per minute (CPM) using a liquid scintillation counter. The open bars represent the proliferation data (Mean ± SEM) of lymphocyte proliferation from patients treated with TAC/MMF/AZA and steroids and closed bars represent data after addition of SRL to TAC (day # 14) without MMF/AZA.
Mentions: The proliferation of lymphocytes from patients treated with TAC and SRL were compared with lymphocytes from patients treated with TAC and MMF/Aza. The results are shown in Figure 2 which, demonstrated a significant inhibition of proliferation of lymphocytes from patients with TAC and SRL compared to TAC plus MMF/Aza. (PHA: 17510 ± 4094 vs 10963 ± 3008 p < 0.05; ConA: 23995 ± 2449 vs 12124 ± 2946 p < 0.006; and anti-CD3: 27089 ± 1557 vs 16093 ± 3097 p < 0.005).

Bottom Line: Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute).RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone.Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine (Nephrology), Medical College of Wisconsin, Milwaukee WI-53226, USA. akkhanna@mcw.edu

ABSTRACT
BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL. Blood was drawn on day zero and 14 days post treatment. Lymphocyte proliferation was quantified by 3H-thymidine uptake assay (results expressed as counts per minute). The mRNA expression was studied by RT-PCR and serum levels of cytokines were quantified by ELISA and a cytokine bead array system. RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone. The mRNA expression of proinflammatory cytokines TNF-alpha (p < 0.05), cyclins G (p < 0.01) and E (p < 05) were decreased, and of TGF-beta (p < 0.03) and p21 (p < 0.05) were increased in patients treated with this combination. Circulating levels of IFN-gamma (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-beta (p < 0.04) was observed in patients treated with TAC and SRL combination. CONCLUSION: These novel findings demonstrate that addition of SRL to TAC therapy enhances immuno modulation and causes increased immunosuppression providing a rationale for this concomitant therapy.

No MeSH data available.


Related in: MedlinePlus